Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001017611 | SCV001178714 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-14 | criteria provided, single submitter | clinical testing | The p.N279S variant (also known as c.836A>G), located in coding exon 6 of the NTHL1 gene, results from an A to G substitution at nucleotide position 836. The asparagine at codon 279 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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. |
Labcorp Genetics |
RCV001067983 | SCV001233070 | uncertain significance | not provided | 2025-01-13 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 279 of the NTHL1 protein (p.Asn279Ser). This variant is present in population databases (rs149287105, gnomAD 0.003%). 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: 822331). 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. |
Gene |
RCV001067983 | SCV002000314 | uncertain significance | not provided | 2021-12-20 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); 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; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
Sema4, |
RCV001017611 | SCV002529025 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-03 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003467640 | SCV004192168 | uncertain significance | Familial adenomatous polyposis 3 | 2023-05-30 | criteria provided, single submitter | clinical testing |