ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6727G>A (p.Gly2243Ser)

gnomAD frequency: 0.00004  dbSNP: rs61751491
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002314178 SCV000738389 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-05 criteria provided, single submitter clinical testing The p.G2243S variant (also known as c.6727G>A), located in coding exon 34 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 6727. The glycine at codon 2243 is replaced by serine, an amino acid with similar properties. This variant was detected in a pediatric patient with T-cell acute lymphoblastic leukemia where NOTCH1 was only partially sequenced and clinical information was not available (Kraszewska MD et al, Blood Cells Mol. Dis. 2013 Jan; 50(1):33-8). This amino acid position is not well conserved in available vertebrate species, and serine 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 RCV001567286 SCV001790942 likely benign not provided 2021-01-27 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001868117 SCV002170682 benign Adams-Oliver syndrome 5 2023-09-23 criteria provided, single submitter clinical testing

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