Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000147564 | SCV000195012 | likely pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2013-08-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000255003 | SCV000322272 | pathogenic | not provided | 2016-12-20 | criteria provided, single submitter | clinical testing | The R1049Q variant in the SMC1A gene has been reported previously as a de novo change in an individual with Cornelia de Lange syndrome (Liu et al., 2009). The R1049Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1049Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. The R1049Q variant maps to the coiled-coil domain, which may interfere with heterodimer formation and disrupt the interaction with other cohesin subunits (Mannini et al., 2010). We interpret R1049Q as a pathogenic variant. |
| Labcorp Genetics |
RCV000147564 | SCV000637995 | pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1049 of the SMC1A protein (p.Arg1049Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Cornelia de Lange syndrome (PMID: 19701948). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 159954). 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 SMC1A protein function. For these reasons, this variant has been classified as Pathogenic. |
| Molecular Genetics Lab, |
RCV003883136 | SCV004697622 | likely pathogenic | Congenital muscular hypertrophy-cerebral syndrome; Developmental and epileptic encephalopathy, 85, with or without midline brain defects | criteria provided, single submitter | clinical testing |