Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000407437 | SCV000338206 | uncertain significance | not provided | 2015-12-07 | criteria provided, single submitter | clinical testing | |
| 3billion, |
RCV002250615 | SCV002521661 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2E | 2022-05-22 | criteria provided, single submitter | clinical testing | Amino acid change identical to known pathogenic variant has been previously reported with supporting evidence; this might be considered evidence of a supporting level (PMID:33250842). It has been reported with an extremely low frequency in the gnomAD v2.1.1 (https://gnomad.broadinstitute.org/) dataset. In silico prediction tools and conservation analysis predicted that this variant was probably damaging to the protein structure/function (REVEL: 0.864>=0.6). herefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. |
| Revvity Omics, |
RCV002250615 | SCV004238649 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2E | 2023-10-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002250615 | SCV004483568 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2E | 2024-05-20 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 116 of the SGCB protein (p.Met116Val). This variant is present in population databases (rs752168132, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 31069529, 33250842; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 285260). 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 not expected to disrupt SGCB protein function with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |