ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2429+14A>C

gnomAD frequency: 0.00014  dbSNP: rs200817451
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037455 SCV000061113 likely benign not specified 2012-03-19 criteria provided, single submitter clinical testing c.2429+14A>C in Intron 20 of MYH6: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 2/7020 European American chromosomes from a broad popula tion by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS;).
GeneDx RCV000037455 SCV000535686 likely benign not specified 2018-02-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000037455 SCV001448372 benign not specified 2020-11-30 criteria provided, single submitter clinical testing Variant summary: MYH6 c.2429+14A>C 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 0.00021 in 251420 control chromosomes, predominantly at a frequency of 0.00036 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 14 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 South Asian origin. To our knowledge, no occurrence of c.2429+14A>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV002054661 SCV002397467 benign Hypertrophic cardiomyopathy 14 2023-09-29 criteria provided, single submitter clinical testing

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