Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001103185 | SCV001259910 | benign | Focal segmental glomerulosclerosis 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Labcorp Genetics |
RCV002556061 | SCV003262763 | uncertain significance | not provided | 2022-10-18 | 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. 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 TRPC6 protein function. ClinVar contains an entry for this variant (Variation ID: 877459). This missense change has been observed in individual(s) with nephrotic syndrome (PMID: 28780565). This variant is present in population databases (rs201522744, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 798 of the TRPC6 protein (p.Asp798His). |