Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002923007 | SCV003265059 | uncertain significance | not provided | 2022-03-15 | 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 591 of the SCNN1A protein (p.Arg591Gln). This variant is present in population databases (rs140175017, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SCNN1A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Johns Hopkins Genomics, |
RCV003229648 | SCV003927228 | uncertain significance | Pseudohypoaldosteronism, type IB1, autosomal recessive | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant (rs140175017) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 42/282386 total alleles; 0.015%; no homozygotes). It has been reported in ClinVar (Variation ID 2056764) but has not been reported in the literature, to our knowledge. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be tolerated. While arginine at this residue is conserved in many of the species assessed, some species have a different amino acid at this position, including two species with glutamine. We consider the clinical significance of c.1772G>A in SCNN1A to be uncertain at this time. |
Fulgent Genetics, |
RCV005010790 | SCV005636524 | uncertain significance | Pseudohypoaldosteronism, type IB1, autosomal recessive; Bronchiectasis with or without elevated sweat chloride 2; Liddle syndrome 3 | 2024-01-18 | criteria provided, single submitter | clinical testing |