Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000703726 | SCV000832640 | uncertain significance | Nephronophthisis-like nephropathy 1 | 2020-02-05 | criteria provided, single submitter | clinical testing | 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 threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with XPNPEP3-related disease. ClinVar contains an entry for this variant (Variation ID: 580250). This variant is present in population databases (rs139592817, ExAC 0.05%). This sequence change replaces alanine with threonine at codon 506 of the XPNPEP3 protein (p.Ala506Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. 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. |
| Illumina Laboratory Services, |
RCV000703726 | SCV001305558 | uncertain significance | Nephronophthisis-like nephropathy 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Fulgent Genetics, |
RCV000703726 | SCV002792810 | uncertain significance | Nephronophthisis-like nephropathy 1 | 2022-02-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002533692 | SCV003697828 | uncertain significance | Inborn genetic diseases | 2021-07-09 | criteria provided, single submitter | clinical testing | The c.1516G>A (p.A506T) alteration is located in exon 10 (coding exon 10) of the XPNPEP3 gene. This alteration results from a G to A substitution at nucleotide position 1516, causing the alanine (A) at amino acid position 506 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |