Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001224383 | SCV001396573 | uncertain significance | Hypertrophic cardiomyopathy | 2019-05-23 | 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. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MYH7-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 611 of the MYH7 protein (p.Lys611Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. |
| Gene |
RCV001544582 | SCV001763738 | likely pathogenic | not provided | 2020-11-13 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 952302; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| 3billion | RCV003152753 | SCV003841427 | likely pathogenic | Hypertrophic cardiomyopathy 1 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PMID: 29300372). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.66; 3Cnet: 0.97). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MYH7 related disorder (ClinVar ID: VCV000952302). A different missense change at the same codon (p.Lys611Gln) has been reported to be associated with MYH7 related disorder (ClinVar ID: VCV000234755). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |