Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002439821 | SCV002746883 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-29 | criteria provided, single submitter | clinical testing | The p.V97D variant (also known as c.290T>A), located in coding exon 2 of the NTHL1 gene, results from a T to A substitution at nucleotide position 290. The valine at codon 97 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003698961 | SCV004464805 | uncertain significance | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 97 of the NTHL1 protein (p.Val97Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1797571). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The aspartic acid 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. |