ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.73A>T (p.Arg25Trp)

dbSNP: rs369039003
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810751 SCV000950984 uncertain significance not provided 2021-06-02 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NTHL1-related disease. ClinVar contains an entry for this variant (Variation ID: 654738). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 33 of the NTHL1 protein (p.Arg33Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan.
Ambry Genetics RCV002381801 SCV002694001 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-24 criteria provided, single submitter clinical testing The p.R33W variant (also known as c.97A>T), located in coding exon 1 of the NTHL1 gene, results from an A to T substitution at nucleotide position 97. The arginine at codon 33 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. 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.

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