Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002366893 | SCV002663274 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-01 | criteria provided, single submitter | clinical testing | The p.A222V variant (also known as c.665C>T), located in coding exon 4 of the NTHL1 gene, results from a C to T substitution at nucleotide position 665. The alanine at codon 222 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003098324 | SCV003212387 | uncertain significance | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 222 of the NTHL1 protein (p.Ala222Val). 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. 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. This variant is not present in population databases (gnomAD no frequency). |