Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Agnes Ginges Centre for Molecular Cardiology, |
RCV000584807 | SCV000692497 | uncertain significance | Hypertrophic cardiomyopathy | 2018-08-22 | criteria provided, single submitter | research | The MYH7 Val338Glu variant is novel. It is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We have identified this variant in a HCM proband that was diagnosed in childhood. In a large HCM population study Walsh et al., showed that MYH7 variants identified in HCM cases were found to cluster between amino acids 181- 937 (2017), this implies that variants in this region are likely to cause a HCM phenotype. Interestingly, rare variants at this position (Val338Ala & Val338Met) have been reported in HCM cases and Val338Met has been classified as 'likely pathogenic'. Computational tools SIFT, PolyPhen-2 and MutationTaster predict this variant to have a deleterious effect. Based on the adapted ACMG guidelines (Kelly MA, et al., 2018) this variant is located in a known functional domain of MYH7 (PM1), is rare in the general population (PM2) and in silico tools predict the variant to be deleterious (PP3), therefore we classify MYH7 Val338Glu as a variant of 'uncertain significance'. |