ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.349C>A (p.Pro117Thr)

dbSNP: rs149277519
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001055409 SCV001219797 uncertain significance not provided 2024-11-28 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 125 of the NTHL1 protein (p.Pro125Thr). This variant is present in population databases (rs149277519, gnomAD 0.01%). This missense change has been observed in individual(s) with esophageal squamous cell carcinoma (PMID: 30833958). ClinVar contains an entry for this variant (Variation ID: 851087). 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001789786 SCV002032288 uncertain significance Familial adenomatous polyposis 3 2021-11-11 criteria provided, single submitter clinical testing The NTHL1 c.373C>A (p.Pro125Thr) missense change has a maximum subpopulation frequency of 0.013% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/16-2096134-G-T?dataset=gnomad_r2_1). Seven of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with NTHL1-related disease. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PP3.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268420 SCV002551605 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002365709 SCV002625706 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-21 criteria provided, single submitter clinical testing The p.P125T variant (also known as c.373C>A), located in coding exon 2 of the NTHL1 gene, results from a C to A substitution at nucleotide position 373. The proline at codon 125 is replaced by threonine, an amino acid with highly similar properties. This alteration has been reported in a patient with esophageal squamous cell carcinoma (Deng J et al. Front Genet, 2019 Feb;10:47). This amino acid position is well 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.
Baylor Genetics RCV001789786 SCV004192152 uncertain significance Familial adenomatous polyposis 3 2024-03-29 criteria provided, single submitter clinical testing

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