ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4372G>A (p.Ala1458Thr)

gnomAD frequency: 0.00010  dbSNP: rs200495793
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468014 SCV000548956 benign Adams-Oliver syndrome 5 2024-01-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV002313172 SCV000739452 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-11-09 criteria provided, single submitter clinical testing The p.A1458T variant (also known as c.4372G>A), located in coding exon 25 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4372. The alanine at codon 1458 is replaced by threonine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs200495793. Based on data from ExAC, the A allele has an overall frequency of <0.01% (7/103644). Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.83% (1/120) Colombian alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.01% (1/12676) total alleles studied and 0.01% (1/8440) European American alleles. 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.
GeneDx RCV001557539 SCV001779314 uncertain significance not provided 2021-08-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID #409073; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918)
Genome-Nilou Lab RCV000468014 SCV002553421 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270506 SCV002553422 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing

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