ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.358C>G (p.Arg120Gly)

gnomAD frequency: 0.00010  dbSNP: rs370228590
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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 RCV000817334 SCV000957888 uncertain significance not provided 2025-01-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 128 of the NTHL1 protein (p.Arg128Gly). This variant is present in population databases (rs370228590, gnomAD 0.03%). 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: 660196). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 RCV001021245 SCV001182833 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-12 criteria provided, single submitter clinical testing The p.R128G variant (also known as c.382C>G), located in coding exon 3 of the NTHL1 gene, results from a C to G substitution at nucleotide position 382. The arginine at codon 128 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not 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.
Sema4, Sema4 RCV001021245 SCV002528966 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-12 criteria provided, single submitter curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153859 SCV003843035 uncertain significance Familial adenomatous polyposis 3 2023-02-10 criteria provided, single submitter clinical testing The NTHL1 c.358C>G (p.Arg120Gly) missense change has a maximum subpopulation frequency of 0.028% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about the effect of this variant on protein function, but 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.
GeneDx RCV000817334 SCV005371222 uncertain significance not provided 2023-06-06 criteria provided, single submitter clinical testing In silico analysis supports a deleterious effect on splicing; 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

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