ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3741G>C (p.Gln1247His)

gnomAD frequency: 0.00002  dbSNP: rs781658171
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000694420 SCV000822866 benign Adams-Oliver syndrome 5 2022-09-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343485 SCV002621232 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-09-30 criteria provided, single submitter clinical testing The p.Q1247H variant (also known as c.3741G>C), located in coding exon 23 of the NOTCH1 gene, results from a G to C substitution at nucleotide position 3741. The glutamine at codon 1247 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. 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 RCV002510959 SCV002820615 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as a germline pathogenic or benign variant to our knowledge; This variant is associated with the following publications: (PMID: 35127508)

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