ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2051-1G>A

gnomAD frequency: 0.00001  dbSNP: rs773772551
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001338736 SCV001532427 uncertain significance Hypertrophic cardiomyopathy 14 2024-01-30 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 17 of the MYH6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH6 cause disease. This variant is present in population databases (rs773772551, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1035818). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV002418994 SCV002728236 uncertain significance Cardiovascular phenotype 2023-11-30 criteria provided, single submitter clinical testing The c.2051-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 16 of the MYH6 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of MYH6 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002476564 SCV002784307 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-09-04 criteria provided, single submitter clinical testing

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