Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001048976 | SCV001213006 | uncertain significance | not provided | 2019-03-26 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with serine at codon 192 of the NTHL1 protein (p.Thr192Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NTHL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002348388 | SCV002648552 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-25 | criteria provided, single submitter | clinical testing | The p.T192S variant (also known as c.574A>T), located in coding exon 4 of the NTHL1 gene, results from an A to T substitution at nucleotide position 574. The threonine at codon 192 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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. |