ClinVar Genomic variation as it relates to human health
NM_000258.3(MYL3):c.235G>A (p.Val79Ile)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000258.3(MYL3):c.235G>A (p.Val79Ile)
Variation ID: 161329 Accession: VCV000161329.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p21.31 3: 46860748 (GRCh38) [ NCBI UCSC ] 3: 46902238 (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 7, 2014 Feb 14, 2024 Dec 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000258.3:c.235G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000249.1:p.Val79Ile missense NC_000003.12:g.46860748C>T NC_000003.11:g.46902238C>T NG_007555.2:g.26422G>A LRG_395:g.26422G>A LRG_395t1:c.235G>A LRG_395p1:p.Val79Ile - Protein change
- V79I
- Other names
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- Canonical SPDI
- NC_000003.12:46860747:C: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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0.00020 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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
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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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MYL3 | No evidence available | No evidence available |
GRCh38 GRCh37 |
372 | 383 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Likely pathogenic (1) |
no assertion criteria provided
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Jun 1, 2014 | RCV000148716.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 1, 2023 | RCV000527113.6 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Dec 26, 2022 | RCV000777873.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 8, 2021 | RCV002453474.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 14, 2023 | RCV003155086.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 7, 2021 | RCV002505134.1 |
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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Uncertain significance
(Nov 24, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001333536.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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Uncertain significance
(Sep 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002735742.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.V79I variant (also known as c.235G>A), located in coding exon 3 of the MYL3 gene, results from a G to A substitution at nucleotide … (more)
The p.V79I variant (also known as c.235G>A), located in coding exon 3 of the MYL3 gene, results from a G to A substitution at nucleotide position 235. The valine at codon 79 is replaced by isoleucine, an amino acid with highly similar properties. This variant was detected in an asymptomatic individual with hypertrophic cardiomyopathy (HCM), as well as in three family members with borderline HCM findings and in six unaffected carrier family members, including some who were children at the time of evaluation (Andersen PS et al. Biochem Res Int, 2012 Apr;2012:685108). This variant has also been reported as a secondary finding in exome cohorts with limited clinical details provided (Lawrence L et al. Genet Med, 2014 Oct;16:741-50; Olfson E et al. PLoS One, 2015 Sep;10:e0135193). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy 8
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002816553.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Feb 14, 2023)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844680.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: MYL3 c.235G>A (p.Val79Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Variant summary: MYL3 c.235G>A (p.Val79Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251470 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.235G>A has been reported in the literature as segregating with disease in at least one family, in which one heterozygous individual was diagnosed with asymptomatic hypertrophic cardiomyopathy (HCM) and 3 additional heterozygotes displayed borderline HCM; unaffected heterozygous carriers in the family were under the age of 30, suggesting this variant may cause late-onset and clinically silent disease (Andersen_2012). Therefore, this report does not provide unequivocal conclusions about association of the variant with Hypertrophic Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. (less)
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Uncertain significance
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000623767.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 79 of the MYL3 protein (p.Val79Ile). … (more)
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 79 of the MYL3 protein (p.Val79Ile). This variant is present in population databases (rs150634297, gnomAD 0.005%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 22957257). ClinVar contains an entry for this variant (Variation ID: 161329). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Dec 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000913880.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces valine with isoleucine at codon 79 of the MYL3 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces valine with isoleucine at codon 79 of the MYL3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with a mild form of late-onset hypertrophic cardiomyopathy (PMID: 22957257). However, three carriers from this family had ECG and/or echocardiographic abnormalities that did not fulfill diagnostic criteria for hypertrophic cardiomyopathy. In addition, five carriers from this family showed normal phenotype. This variant has been identified in 7/251470 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Likely pathogenic
(Jun 01, 2014)
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no assertion criteria provided
Method: research
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Cardiomyopathy, hypertrophic
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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CSER _CC_NCGL, University of Washington
Study: ESP 6500 variant annotation
Accession: SCV000190447.1 First in ClinVar: Dec 07, 2014 Last updated: Dec 07, 2014 |
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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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Signal-to-Noise Analysis Can Inform the Likelihood That Incidentally Identified Variants in Sarcomeric Genes Are Associated with Pediatric Cardiomyopathy. | Kurzlechner LM | Journal of personalized medicine | 2022 | PMID: 35629155 |
Identification of Medically Actionable Secondary Findings in the 1000 Genomes. | Olfson E | PloS one | 2015 | PMID: 26332594 |
The implications of familial incidental findings from exome sequencing: the NIH Undiagnosed Diseases Program experience. | Lawrence L | Genetics in medicine : official journal of the American College of Medical Genetics | 2014 | PMID: 24784157 |
Cardiomyopathies: classification, clinical characterization, and functional phenotypes. | Szczesna-Cordary D | Biochemistry research international | 2012 | PMID: 23304510 |
A novel Myosin essential light chain mutation causes hypertrophic cardiomyopathy with late onset and low expressivity. | Andersen PS | Biochemistry research international | 2012 | PMID: 22957257 |
Text-mined citations for rs150634297 ...
HelpRecord last updated Feb 20, 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.