ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4918G>A (p.Ala1640Thr)

gnomAD frequency: 0.00003  dbSNP: rs976118697
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544764 SCV000659451 benign Adams-Oliver syndrome 5 2023-07-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002350401 SCV002645439 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-12-16 criteria provided, single submitter clinical testing The p.A1640T variant (also known as c.4918G>A), located in coding exon 26 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4918. The alanine at codon 1640 is replaced by threonine, an amino acid with similar properties. This variant was detected in a family with congenital heart defects; however, details were limited and other potentially causative variants were detected in affected members (Jia Y et al. Am J Med Genet A, 2015 Aug;167A:1822-9). This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other vertebrate species. 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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