Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001041618 | SCV001205242 | uncertain significance | not provided | 2019-04-03 | criteria provided, single submitter | clinical testing | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NTHL1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 281 of the NTHL1 protein (p.Leu281Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. |
| Ambry Genetics | RCV004031255 | SCV005019857 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-09 | criteria provided, single submitter | clinical testing | The p.L281F variant (also known as c.841C>T), located in coding exon 6 of the NTHL1 gene, results from a C to T substitution at nucleotide position 841. The leucine at codon 281 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |