Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000628849 | SCV000749756 | uncertain significance | Hypertrophic cardiomyopathy | 2019-06-11 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 970 of the MYH7 protein (p.Ala970Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. 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 different missense substitution at this codon (p.Ala970Val) has been reported in an individual affected with dilated cardiomyopathy (PMID: 19412328). 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 disease. This variant is not present in population databases (ExAC no frequency). |
Color Diagnostics, |
RCV003532209 | SCV004356898 | uncertain significance | Cardiomyopathy | 2023-05-11 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with serine at codon 970 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 1/251440 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |