Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039126 | SCV001202638 | uncertain significance | Nephronophthisis | 2022-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 659 of the INVS protein (p.Arg659Lys). This variant is present in population databases (rs201738845, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with INVS-related conditions. ClinVar contains an entry for this variant (Variation ID: 837729). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine 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. |
| Fulgent Genetics, |
RCV002479249 | SCV002784695 | uncertain significance | Infantile nephronophthisis | 2021-10-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002551440 | SCV003646431 | uncertain significance | Inborn genetic diseases | 2022-10-06 | criteria provided, single submitter | clinical testing | The c.1976G>A (p.R659K) alteration is located in exon 13 (coding exon 12) of the INVS gene. This alteration results from a G to A substitution at nucleotide position 1976, causing the arginine (R) at amino acid position 659 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |