Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001062099 | SCV001226875 | uncertain significance | not provided | 2024-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 125 of the NTHL1 protein (p.Pro125Gln). This variant is present in population databases (rs777263711, gnomAD 0.006%). 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: 856602). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV002348448 | SCV002621255 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-13 | criteria provided, single submitter | clinical testing | The p.P125Q variant (also known as c.374C>A), located in coding exon 2 of the NTHL1 gene, results from a C to A substitution at nucleotide position 374. The proline at codon 125 is replaced by glutamine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001062099 | SCV004014547 | uncertain significance | not provided | 2023-01-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27397505) |
| Baylor Genetics | RCV004570255 | SCV005053710 | uncertain significance | Familial adenomatous polyposis 3 | 2024-03-29 | criteria provided, single submitter | clinical testing |