Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000628862 | SCV000749770 | uncertain significance | Hypertrophic cardiomyopathy | 2018-02-15 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tryptophan at codon 4 of the MYH7 protein (p.Ser4Trp). The serine residue is weakly conserved and there is a large physicochemical difference between serine and tryptophan. 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. A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be tolerated. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). This variant has not been reported in the literature in individuals with MYH7-related disease. However, a different sequence change affecting the same codon, p.Ser4Leu, has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 19150014, 22765922, 25342278). |