ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4685G>T (p.Arg1562Leu)

dbSNP: rs371068881
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV001089614 SCV001245090 uncertain significance Hypertrophic cardiomyopathy 2018-10-16 criteria provided, single submitter research MYH6 Arg1562Leu has not been previously reported but is present in population databases such as the Genome Aggregation Database (AF= 0.000002; http://gnomad.broadinstitute.org/). We identified this variant in HCM proband with no family history of disease. In silico tools SIFT, MutationTaster and PolyPhen2 predict this variant to be deleterious. Based on this information we classify this as a variant of 'uncertain significance'.
Labcorp Genetics (formerly Invitae), Labcorp RCV001322572 SCV001513449 uncertain significance Hypertrophic cardiomyopathy 14 2022-03-05 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 870081). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1562 of the MYH6 protein (p.Arg1562Leu).
AiLife Diagnostics, AiLife Diagnostics RCV002223267 SCV002501144 uncertain significance not provided 2022-03-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV002339390 SCV002636281 uncertain significance Cardiovascular phenotype 2022-12-23 criteria provided, single submitter clinical testing The p.R1562L variant (also known as c.4685G>T), located in coding exon 31 of the MYH6 gene, results from a G to T substitution at nucleotide position 4685. The arginine at codon 1562 is replaced by leucine, an amino acid with dissimilar properties. A different variant affecting this codon (p.R1562W, c.4684C>T) has been detected in a hypertrophic cardiomyopathy cohort; however, details were limited (Mademont-Soler I et al. PLoS ONE, 2017 Aug;12:e0181465). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002482159 SCV002791473 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-07-16 criteria provided, single submitter clinical testing

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