ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.443C>T (p.Ala148Val)

gnomAD frequency: 0.00001  dbSNP: rs748576083
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000796990 SCV000936526 uncertain significance not provided 2025-01-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 156 of the NTHL1 protein (p.Ala156Val). This variant is present in population databases (rs748576083, gnomAD 0.003%). 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: 643316). 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.
GeneDx RCV000796990 SCV002000650 uncertain significance not provided 2022-07-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002334490 SCV002640306 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-03 criteria provided, single submitter clinical testing The p.A156V variant (also known as c.467C>T), located in coding exon 3 of the NTHL1 gene, results from a C to T substitution at nucleotide position 467. The alanine at codon 156 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003321737 SCV004027028 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003411752 SCV004109225 uncertain significance NTHL1-related disorder 2023-01-20 criteria provided, single submitter clinical testing The NTHL1 c.467C>T variant is predicted to result in the amino acid substitution p.Ala156Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0036% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-2094713-G-A), and it is classified as having uncertain clinical significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/643316/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003467360 SCV004192150 uncertain significance Familial adenomatous polyposis 3 2024-02-08 criteria provided, single submitter clinical testing

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