Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV000790349 | SCV000891142 | likely pathogenic | MYH9-related disorder | 2018-12-12 | criteria provided, single submitter | research | PS4_supporting, PM2, PP4, PP3 |
ISTH- |
RCV002245639 | SCV002515668 | likely pathogenic | Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV003558559 | SCV004298870 | likely pathogenic | not provided | 2023-08-07 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH9 protein function. ClinVar contains an entry for this variant (Variation ID: 623105). This missense change has been observed in individuals with clinical features of MYH9-related conditions (PMID: 26382273, 28983057, 31562665, 32581362, 33718801; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 74 of the MYH9 protein (p.Lys74Glu). |