Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000015206 | SCV000998857 | uncertain significance | Arthrogryposis, distal, type 2B3 | 2019-08-21 | criteria provided, single submitter | curation | This variant is interpreted as a variant of uncertain significance for Arthrogryposis, distal, 2B3, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PP3, PM1. |
Gene |
RCV001650833 | SCV001871152 | likely pathogenic | not provided | 2023-10-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31030430, 19309503, 29625835, 17380469, 16642020, 26578207) |
Revvity Omics, |
RCV001650833 | SCV002017664 | pathogenic | not provided | 2021-02-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001650833 | SCV003441669 | uncertain significance | not provided | 2022-06-07 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 14143). This missense change has been observed in individuals with distal arthrogryposis (PMID: 16642020, 26578207, 31030430). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 375 of the MYH3 protein (p.Glu375Lys). |
Prevention |
RCV004532359 | SCV004118288 | likely pathogenic | MYH3-related disorder | 2022-10-06 | criteria provided, single submitter | clinical testing | The MYH3 c.1123G>A variant is predicted to result in the amino acid substitution p.Glu375Lys. This variant has been reported in the heterozygous state in at least one family with distal arthrogryposis (reported as 1192G>A, p.Glu375Lys in Toydemir et al. 2006. PubMed ID: 16642020). At PreventionGenetics, we have observed this variant in the heterozygous state in additional individuals with distal arthrogryposis (Internal Data, PreventionGenetics). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic for autosomal dominant distal arthrogryposis. |
OMIM | RCV000015206 | SCV000035463 | pathogenic | Arthrogryposis, distal, type 2B3 | 2006-05-01 | no assertion criteria provided | literature only |