ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.1295C>G (p.Thr432Arg)

dbSNP: rs200562991
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001733349 SCV001982116 uncertain significance not provided 2021-09-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV002539825 SCV003023384 uncertain significance Adams-Oliver syndrome 5 2022-03-21 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1301299). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 432 of the NOTCH1 protein (p.Thr432Arg).
Ambry Genetics RCV004651703 SCV005142219 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-06-04 criteria provided, single submitter clinical testing The p.T432R variant (also known as c.1295C>G), located in coding exon 8 of the NOTCH1 gene, results from a C to G substitution at nucleotide position 1295. The threonine at codon 432 is replaced by arginine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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