Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Cavalleri Lab, |
RCV001031001 | SCV001160788 | likely pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2019-12-11 | criteria provided, single submitter | research | ACMG evidence PS2, PM2, PP2, PP3 |
Invitae | RCV001031001 | SCV001396292 | pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 983 of the SMC1A protein (p.Tyr983Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SMC1A-related conditions (PMID: 32238909). In at least one individual the variant was observed to be de novo. This variant is also known as c.2882A>G (p.Y961C). ClinVar contains an entry for this variant (Variation ID: 812178). 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 expected to disrupt SMC1A protein function. For these reasons, this variant has been classified as Pathogenic. |