Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001220479 | SCV001392471 | uncertain significance | not provided | 2025-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 298 of the NTHL1 protein (p.His298Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of NTHL1-associated polyposis (internal data). ClinVar contains an entry for this variant (Variation ID: 949091). 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 tolerated. 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 | RCV002375199 | SCV002687424 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-07 | criteria provided, single submitter | clinical testing | The p.H298R variant (also known as c.893A>G), located in coding exon 6 of the NTHL1 gene, results from an A to G substitution at nucleotide position 893. The histidine at codon 298 is replaced by arginine, an amino acid with highly similar 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. |