ClinVar Genomic variation as it relates to human health
NM_001145809.2(MYH14):c.1150G>T (p.Gly384Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(1); Benign(2); Likely benign(8)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001145809.2(MYH14):c.1150G>T (p.Gly384Cys)
Variation ID: 2199 Accession: VCV000002199.41
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19q13.33 19: 50244277 (GRCh38) [ NCBI UCSC ] 19: 50747534 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 26, 2014 May 12, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001145809.2:c.1150G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001139281.1:p.Gly384Cys missense NM_001077186.2:c.1150G>T NP_001070654.1:p.Gly384Cys missense NM_024729.4:c.1126G>T NP_079005.3:p.Gly376Cys missense NC_000019.10:g.50244277G>T NC_000019.9:g.50747534G>T NG_011645.1:g.45650G>T - Protein change
- G376C, G384C
- Other names
- -
- Canonical SPDI
- NC_000019.10:50244276:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00240 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00219
1000 Genomes Project 0.00240
Exome Aggregation Consortium (ExAC) 0.00286
Trans-Omics for Precision Medicine (TOPMed) 0.00301
The Genome Aggregation Database (gnomAD) 0.00303
The Genome Aggregation Database (gnomAD), exomes 0.00304
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MYH14 | - | - |
GRCh38 GRCh37 |
1191 | 1225 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000002283.15 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Apr 27, 2019 | RCV000037022.25 | |
Benign/Likely benign (8) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000438830.32 | |
Likely benign (1) |
criteria provided, single submitter
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May 4, 2023 | RCV003993731.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Sep 13, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000331450.4
First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Likely benign
(Apr 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
unknown
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000930197.1
First in ClinVar: Aug 04, 2019 Last updated: Aug 04, 2019 |
Geographic origin: Iran
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Benign
(Jul 05, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000060678.5
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
p.Gly384Cys in exon 11 of MYH14: This variant is not expected to have clinical s ignificance, because it has been identified in 1.3% (136/10142) of … (more)
p.Gly384Cys in exon 11 of MYH14: This variant is not expected to have clinical s ignificance, because it has been identified in 1.3% (136/10142) of Ashkenazi Jew ish chromosomes including 1 homozygote by the Genome Aggregation Database (gnomA D, http://gnomad.broadinstitute.org/; dbSNP rs119103280). Although this variant has been reported as a de novo variant in one individual with moderate sensorine ural hearing loss (Donaudy 2004), the evidence is not sufficient to establish ca usality. (less)
Number of individuals with the variant: 19
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 4A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001296271.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(May 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
Affected status: yes
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812390.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
European Non-Finnish population allele frequency is 0.3994% (rs119103280, 511/127.956 alleles, 1 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, … (more)
European Non-Finnish population allele frequency is 0.3994% (rs119103280, 511/127.956 alleles, 1 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as LIKELY BENIGN. Following criteria are met: BS1 (less)
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Likely benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV003918161.8
First in ClinVar: Apr 23, 2023 Last updated: May 12, 2024 |
Comment:
MYH14: BS2
Number of individuals with the variant: 8
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Likely Benign
(Jan 05, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000511768.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Converted during submission to Likely benign.
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Likely benign
(Jul 08, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV001144619.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
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Likely benign
(Feb 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000729165.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 27391121, 25262649, 30622556, 15015131, 27884173, 25098841, 30245029, 31898538)
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Likely benign
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001102482.4
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Benign
(Oct 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157316.3
First in ClinVar: Feb 09, 2020 Last updated: Feb 20, 2024 |
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Pathogenic
(Apr 01, 2004)
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no assertion criteria provided
Method: literature only
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DEAFNESS, AUTOSOMAL DOMINANT 4A
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022441.2
First in ClinVar: Apr 04, 2013 Last updated: Dec 26, 2014 |
Comment on evidence:
In a 9-year-old Italian patient with autosomal dominant nonsyndromic sensorineural hearing loss (DFNA4A; 600652), Donaudy et al. (2004) identified a 1126G-T transversion in exon 9 … (more)
In a 9-year-old Italian patient with autosomal dominant nonsyndromic sensorineural hearing loss (DFNA4A; 600652), Donaudy et al. (2004) identified a 1126G-T transversion in exon 9 of the MYH14 gene, resulting in a gly376-to-cys (G376C) change in the motor domain of the protein. The patient apparently represented a de novo mutation. The patient had a moderate bilateral sensorineural hearing loss without vestibular involvement. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001920105.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001970131.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4). | Donaudy F | American journal of human genetics | 2004 | PMID: 15015131 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYH14 | - | - | - | - |
Text-mined citations for rs119103280 ...
HelpRecord last updated May 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.