ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5224G>T (p.Ala1742Ser)

gnomAD frequency: 0.00008  dbSNP: rs760669267
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000428861 SCV000536587 uncertain significance not provided 2024-03-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in a patient with a connective tissue disorder who harbored a second variant in the DCHS1 gene (PMID: 30675029); This variant is associated with the following publications: (PMID: 30675029, 37839360, 38100419)
Labcorp Genetics (formerly Invitae), Labcorp RCV000471204 SCV000548919 likely benign Adams-Oliver syndrome 5 2025-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002339103 SCV002640627 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-12-29 criteria provided, single submitter clinical testing The p.A1742S variant (also known as c.5224G>T), located in coding exon 28 of the NOTCH1 gene, results from a G to T substitution at nucleotide position 5224. The alanine at codon 1742 is replaced by serine, an amino acid with similar properties. This variant was reported in an individual in a hereditary aortopathy cohort, but the clinical details were limited (Renner S et al. Genet Med, 2019 Aug;21:1832-1841). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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