Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794945 | SCV000934382 | uncertain significance | Hypertrophic cardiomyopathy | 2018-09-17 | criteria provided, single submitter | clinical testing | 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). This variant has been observed in several individuals affected with hypertrophic cardiomyopathy (PMID: 27532257, 23782526). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with serine at codon 355 of the MYH7 protein (p.Ala355Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. Variants that disrupt the p.Ala355 amino acid residue in MYH7 have been observed in affected individuals (PMID: 27247418, 23283745, 21835320, 18761664, 20031618, 24704860, 12707239). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. |