ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.32G>A (p.Arg11Gln)

gnomAD frequency: 0.00001  dbSNP: rs372992221
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000792050 SCV000931322 uncertain significance not provided 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 19 of the NTHL1 protein (p.Arg19Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 639293). 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 disruptive. Experimental studies have shown that this missense change does not substantially affect NTHL1 function (PMID: 30552997). 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 RCV001024430 SCV001186447 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-27 criteria provided, single submitter clinical testing The c.56G>A (p.R19Q) alteration is located in exon 1 (coding exon 1) of the NTHL1 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000792050 SCV001804130 uncertain significance not provided 2022-01-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Published functional studies demonstrate no damaging effect: DNA glycosylase activity comparable to wild type (Shinmura 2018); This variant is associated with the following publications: (PMID: 30552997)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000792050 SCV002010422 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001024430 SCV002528990 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-29 criteria provided, single submitter curation
Baylor Genetics RCV003467330 SCV004192130 uncertain significance Familial adenomatous polyposis 3 2024-03-11 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV003467330 SCV005642837 uncertain significance Familial adenomatous polyposis 3 2024-02-29 criteria provided, single submitter clinical testing

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