ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5398G>A (p.Ala1800Thr)

gnomAD frequency: 0.00002  dbSNP: rs569203312
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315076 SCV000739393 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-01-25 criteria provided, single submitter clinical testing The p.A1800T variant (also known as c.5398G>A), located in coding exon 29 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 5398. The alanine at codon 1800 is replaced by threonine, an amino acid with similar properties. Based on data from ExAC, the A allele was reported in 1 of 118930 (0.0008%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed January 25, 2016]). This variant was previously reported in the SNPDatabase as rs569203312. This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. In the ESP, this variant was not observed in 6043 samples (12086 alleles) with coverage at this position. This amino acid position is poorly conserved on limited sequence alignment; however, 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 variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001219139 SCV001391060 benign Adams-Oliver syndrome 5 2024-08-31 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001219139 SCV002553357 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270876 SCV002553359 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV004767444 SCV005378432 uncertain significance not provided 2023-11-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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