Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002943505 | SCV003279098 | uncertain significance | not provided | 2022-04-12 | 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. Experimental studies have shown that this missense change affects TRPC6 function (PMID: 26147534). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with focal segmental glomerulosclerosis (PMID: 26147534). This variant is present in population databases (rs754919065, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 68 of the TRPC6 protein (p.Arg68Trp). |
Prevention |
RCV003409990 | SCV004106288 | uncertain significance | TRPC6-related disorder | 2023-07-12 | criteria provided, single submitter | clinical testing | The TRPC6 c.202C>T variant is predicted to result in the amino acid substitution p.Arg68Trp. This variant was reported in three individuals from a family with hematuria, proteinuria or FSGS, but was also observed in asymptomatic individuals (Sun et al 2015. PubMed ID: 26147534). This variant is reported in 0.040% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-101375498-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |