Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV002226093 | SCV002504370 | likely pathogenic | not provided | 2024-11-11 | criteria provided, single submitter | clinical testing | Observed in hemizygous and heterozygous state in individuals from a cohort with SMC1A variants; detailed clinical information was not provided (PMID: 28548707); Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; 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: 28548707) |
| Labcorp Genetics |
RCV003089206 | SCV003445241 | uncertain significance | Congenital muscular hypertrophy-cerebral syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 635 of the SMC1A protein (p.Arg635His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with SMC1A-related conditions (PMID: 28548707). ClinVar contains an entry for this variant (Variation ID: 1678779). 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 with a positive predictive value of 80%. 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. |