ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.670A>C (p.Thr224Pro)

dbSNP: rs2084297825
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001240161 SCV001413085 uncertain significance not provided 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 232 of the NTHL1 protein (p.Thr232Pro). This variant is not present in population databases (gnomAD no frequency). 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: 965657). 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 RCV002366058 SCV002664355 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-18 criteria provided, single submitter clinical testing The p.T232P variant (also known as c.694A>C), located in coding exon 4 of the NTHL1 gene, results from an A to C substitution at nucleotide position 694. The threonine at codon 232 is replaced by proline, an amino acid with highly 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV005055160 SCV005689183 uncertain significance Familial adenomatous polyposis 3 2025-02-05 criteria provided, single submitter clinical testing The NTHL1 c.670A>C (p.Thr224Pro) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with NTHL1-associated polyposis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV004731108 SCV005339635 uncertain significance NTHL1-related disorder 2024-07-29 no assertion criteria provided clinical testing The NTHL1 c.694A>C variant is predicted to result in the amino acid substitution p.Thr232Pro. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/965657/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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