Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001952938 | SCV002221923 | uncertain significance | Autosomal recessive polycystic kidney disease | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with arginine at codon 3222 of the PKHD1 protein (p.His3222Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs777989032, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. 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 arginine 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. |
| Ambry Genetics | RCV004043179 | SCV005005336 | likely benign | Inborn genetic diseases | 2024-02-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |