Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002512990 | SCV003441357 | uncertain significance | Nephronophthisis | 2022-05-24 | 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 INVS function (PMID: 15852005). 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 11960). This missense change has been observed in individual(s) with clinical features of nephronophthisis (PMID: 12872123). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 493 of the INVS protein (p.Leu493Ser). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689414 | SCV005185961 | uncertain significance | not specified | 2024-05-31 | criteria provided, single submitter | clinical testing | Variant summary: INVS c.1478T>C (p.Leu493Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251456 control chromosomes (gnomAD). c.1478T>C has been reported in the literature in at least one homozygous individual affected with Infantile Nephronophthisis (Otto_2003). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Simons_2005). The following publications have been ascertained in the context of this evaluation (PMID: 21866095, 12872123, 15852005, 19177160). ClinVar contains an entry for this variant (Variation ID: 11960). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000012738 | SCV000032973 | pathogenic | Infantile nephronophthisis | 2003-08-01 | no assertion criteria provided | literature only |