ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6481C>T (p.Pro2161Ser)

gnomAD frequency: 0.00003  dbSNP: rs201518848
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727124 SCV000617310 uncertain significance not provided 2023-08-11 criteria provided, single submitter clinical testing Reported in an individual with bicuspid aortic valve (Bonachea et al., 2014); 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: 25260786, 31624253)
Eurofins Ntd Llc (ga) RCV000727124 SCV000705953 uncertain significance not provided 2017-03-17 criteria provided, single submitter clinical testing
Invitae RCV001058437 SCV001223010 benign Adams-Oliver syndrome 5 2024-01-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV001335846 SCV001529089 uncertain significance Aortic valve disease 1 2018-04-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab RCV001058437 SCV002553300 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001335846 SCV002553301 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002367728 SCV002660761 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-10-06 criteria provided, single submitter clinical testing The p.P2161S variant (also known as c.6481C>T), located in coding exon 34 of the NOTCH1 gene, results from a C to T substitution at nucleotide position 6481. The proline at codon 2161 is replaced by serine, an amino acid with similar properties. This variant was identified in a cohort of individuals with bicuspid aortic valve and in an individual with heterotaxy (Bonachea EM et al. BMC Med Genomics, 2014 Sep;7:56; Watkins WS et al. Nat Commun. 2019 10;10(1):4722). This amino acid position is well 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 RCV002481696 SCV002779589 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2022-04-26 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001535474 SCV001749401 not provided Adams-Oliver syndrome 5; Aortic valve disorder no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 12-27-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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