ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4472C>T (p.Thr1491Met)

gnomAD frequency: 0.00001  dbSNP: rs369915496
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000471927 SCV000548942 benign Adams-Oliver syndrome 5 2023-10-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV002313171 SCV000739410 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-03-09 criteria provided, single submitter clinical testing The p.T1491M variant (also known as c.4472C>T), located in coding exon 25 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 4472. The threonine at codon 1491 is replaced by methionine, an amino acid with some similar properties. This alteration has been reported in one patient with bicuspid aortic valve (BAV) (Dargis N, Am. J. Cardiol. 2016 Feb; 117(3):420-6). This variant was previously reported in the SNPDatabase as rs369915496. Based on data from ExAC, the T allele has an overall frequency of less than 0.01% (2/103014). Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.01% (1/12820) total alleles studied and 0.01% (1/8502) European American alleles. This amino acid position is poorly conserved in available 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.
Fulgent Genetics, Fulgent Genetics RCV000766058 SCV000897514 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001580497 SCV001817922 uncertain significance not provided 2023-08-31 criteria provided, single submitter clinical testing Has been reported in an individual with Bicuspid Aortic Valve (BAV) (Dargis et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26708639)
Genome-Nilou Lab RCV000471927 SCV002553414 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270500 SCV002553416 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing

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