Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001346984 | SCV001541222 | uncertain significance | not provided | 2024-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 301 of the NTHL1 protein (p.Leu301Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1042949). 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 | RCV002377473 | SCV002686604 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-26 | criteria provided, single submitter | clinical testing | The p.L301F variant (also known as c.901C>T), located in coding exon 6 of the NTHL1 gene, results from a C to T substitution at nucleotide position 901. The leucine at codon 301 is replaced by phenylalanine, 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001346984 | SCV005623940 | uncertain significance | not provided | 2024-07-03 | criteria provided, single submitter | clinical testing | The NTHL1 c.901C>T (p.Leu301Phe) variant has not been reported in individuals with NTHL1-related conditions in the published literature. The frequency of this variant in the general population, 0.0000041 (1/243490 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |