ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.644A>G (p.His215Arg)

dbSNP: rs2084298229
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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 RCV001060886 SCV001225603 uncertain significance not provided 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 223 of the NTHL1 protein (p.His223Arg). 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: 855591). 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 RCV001060886 SCV001824646 uncertain significance not provided 2019-07-25 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics RCV002365736 SCV002664861 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-18 criteria provided, single submitter clinical testing The p.H223R variant (also known as c.668A>G), located in coding exon 4 of the NTHL1 gene, results from an A to G substitution at nucleotide position 668. The histidine at codon 223 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003467810 SCV004192142 uncertain significance Familial adenomatous polyposis 3 2023-08-06 criteria provided, single submitter clinical testing

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