ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2161C>T (p.Arg721Trp)

gnomAD frequency: 0.00002  dbSNP: rs387906656
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001203574 SCV001374747 uncertain significance Hypertrophic cardiomyopathy 14 2023-01-02 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. Experimental studies have shown that this missense change affects MYH6 function (PMID: 25717017). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 29799). This missense change has been observed in individual(s) with atrial fibrillation, coarctation of the aorta, and/or sick sinus syndrome (PMID: 21378987, 29050564, 29590334). This variant is present in population databases (rs387906656, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 721 of the MYH6 protein (p.Arg721Trp).
Revvity Omics, Revvity RCV003129755 SCV003809560 uncertain significance not provided 2021-07-23 criteria provided, single submitter clinical testing
GeneDx RCV003129755 SCV005201618 uncertain significance not provided 2024-02-24 criteria provided, single submitter clinical testing Reported in individuals with various cardiac conditions including sick sinus syndrome, atrial fibrillation, and left-sided cardiac malformations such as coarctation of the aorta and hypoplastic left heart syndrome (PMID: 29511194, 21378987, 29050564, 29590334, 29697798, 35621855); Described as an Icelandic founder variant (PMID: 21378987, 29590334); Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest a damaging effect on protein function (PMID: 25717017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35784482, 24020943, 22939045, 33580673, 29050564, 26284702, 29590334, 29697798, 35621855, 35159226, 29511194, 21378987, 25717017)
OMIM RCV000022669 SCV000043958 risk factor Sick sinus syndrome 3, susceptibility to 2011-03-06 no assertion criteria provided literature only

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