ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3979-15C>A

gnomAD frequency: 0.00146  dbSNP: rs529249069
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001255577 SCV001432070 benign not specified 2020-08-31 criteria provided, single submitter clinical testing Variant summary: MYH6 c.3979-15C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00038 in 225090 control chromosomes, predominantly at a frequency of 0.0038 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 150-fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.3979-15C>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001812263 SCV001473288 benign not provided 2020-01-16 criteria provided, single submitter clinical testing
Invitae RCV002069360 SCV002409158 benign Hypertrophic cardiomyopathy 14 2024-01-22 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004538539 SCV004738589 likely benign MYH6-related disorder 2021-03-08 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center RCV001255577 SCV001921277 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001255577 SCV001929022 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001255577 SCV001976055 benign not specified no assertion criteria provided clinical testing

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