ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4078G>A (p.Gly1360Ser)

gnomAD frequency: 0.00003  dbSNP: rs769493139
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002310901 SCV000319441 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2015-02-23 criteria provided, single submitter clinical testing The p.G1360S variant (also known as c.4078G>A), located in coding exon 25 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4078. The glycine at codon 1360 is replaced by serine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5298 samples (10596 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Blueprint Genetics RCV000788669 SCV000927860 uncertain significance not provided 2018-08-16 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270153 SCV002553436 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270152 SCV002553438 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002270153 SCV003514769 benign Adams-Oliver syndrome 5 2023-11-16 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000788669 SCV004162026 uncertain significance not provided 2022-10-01 criteria provided, single submitter clinical testing NOTCH1: PP2
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000788669 SCV001956235 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000788669 SCV001964364 uncertain significance not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004734901 SCV005362315 uncertain significance NOTCH1-related disorder 2024-07-20 no assertion criteria provided clinical testing The NOTCH1 c.4078G>A variant is predicted to result in the amino acid substitution p.Gly1360Ser. This variant has been reported in a patient with a congenital heart defect (Blue et al 2014. PubMed ID: 25500235). This variant is reported in 0.0090% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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