Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Pediatric Genomic Medicine, |
RCV000424167 | SCV000511082 | uncertain significance | not provided | 2016-10-17 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
NIHR Bioresource Rare Diseases, |
RCV000790339 | SCV000891132 | uncertain significance | MYH9-related disorder | 2018-12-12 | criteria provided, single submitter | research | PM6, PM2, PP3, PP4 |
Labcorp Genetics |
RCV000424167 | SCV002211769 | pathogenic | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 41 of the MYH9 protein (p.Phe41Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with MYH9-related disease (PMID: 31562665). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 377017). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH9 protein function. This variant disrupts the p.Phe41 amino acid residue in MYH9. Other variant(s) that disrupt this residue have been observed in individuals with MYH9-related conditions (PMID: 30916803), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |