ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.252G>C (p.Trp84Cys)

gnomAD frequency: 0.00002  dbSNP: rs372698989
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000812392 SCV000952703 uncertain significance not provided 2025-02-03 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 92 of the NTHL1 protein (p.Trp92Cys). This variant is present in population databases (rs372698989, gnomAD 0.008%). This missense change has been observed in individual(s) with adenomatous polyps (PMID: 37834005). ClinVar contains an entry for this variant (Variation ID: 656073). 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 disruptive. 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.
Sema4, Sema4 RCV002255533 SCV002528948 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-25 criteria provided, single submitter curation
Ambry Genetics RCV002255533 SCV002747203 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-16 criteria provided, single submitter clinical testing The p.W92C variant (also known as c.276G>C), located in coding exon 2 of the NTHL1 gene, results from a G to C substitution at nucleotide position 276. The tryptophan at codon 92 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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.
GeneDx RCV000812392 SCV004022828 uncertain significance not provided 2023-07-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000812392 SCV004222195 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000023 (3/128714 chromosomes, http://gnomad.broadinstitute.org), is uninformative in 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 predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Baylor Genetics RCV004569680 SCV005053742 uncertain significance Familial adenomatous polyposis 3 2024-01-11 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.