Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021244 | SCV001182832 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-09 | criteria provided, single submitter | clinical testing | The p.R128S variant (also known as c.382C>A), located in coding exon 3 of the NTHL1 gene, results from a C to A substitution at nucleotide position 382. The arginine at codon 128 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not 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. |
| Labcorp Genetics |
RCV003679028 | SCV004406469 | uncertain significance | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 824271). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 128 of the NTHL1 protein (p.Arg128Ser). |