ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.735+16C>T

gnomAD frequency: 0.00080  dbSNP: rs76202841
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000612074 SCV000719691 benign not specified 2017-06-26 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 RCV000612074 SCV001442717 benign not specified 2020-10-26 criteria provided, single submitter clinical testing Variant summary: MYH6 c.735+16C>T 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 0.0024 in 251488 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 94- fold the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.735+16C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001727769 SCV001471713 benign not provided 2021-09-13 criteria provided, single submitter clinical testing
Invitae RCV002063286 SCV002408815 benign Hypertrophic cardiomyopathy 14 2024-01-17 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000612074 SCV001924345 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000612074 SCV001926344 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001727769 SCV001975560 likely benign not provided no assertion criteria provided clinical testing

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