ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.20G>C (p.Arg7Thr)

gnomAD frequency: 0.00002  dbSNP: rs930166212
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000822195 SCV000962986 uncertain significance not provided 2025-02-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 15 of the NTHL1 protein (p.Arg15Thr). 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: 664161). 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.
GeneDx RCV000822195 SCV001824512 uncertain significance not provided 2024-04-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Sema4, Sema4 RCV002255542 SCV002528973 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-22 criteria provided, single submitter curation
Ambry Genetics RCV002255542 SCV002639699 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-11 criteria provided, single submitter clinical testing The p.R15T variant (also known as c.44G>C), located in coding exon 1 of the NTHL1 gene, results from a G to C substitution at nucleotide position 44. The arginine at codon 15 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002478924 SCV002788582 uncertain significance Familial adenomatous polyposis 3 2021-10-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003396453 SCV004104046 uncertain significance NTHL1-related disorder 2022-09-29 criteria provided, single submitter clinical testing The NTHL1 c.44G>C variant is predicted to result in the amino acid substitution p.Arg15Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.064% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2097805-C-G) and in ClinVar this variant has been interpreted as uncertain (https://ncbi.nlm.nih.gov/clinvar/variation/664161/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV002478924 SCV004192119 uncertain significance Familial adenomatous polyposis 3 2023-12-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000822195 SCV004222207 uncertain significance not provided 2024-09-11 criteria provided, single submitter clinical testing The NTHL1 c.44G>C (p.Arg15Thr) variant has not been reported in individuals with NTHL1-related conditions in the published literature. The frequency of this variant in the general population, 0.000032 (1/31390 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 benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493744 SCV004242669 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing

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