ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3190G>A (p.Asp1064Asn)

gnomAD frequency: 0.00001  dbSNP: rs375931404
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538087 SCV000659419 likely benign Adams-Oliver syndrome 5 2024-09-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001201312 SCV001372451 uncertain significance not specified 2020-06-25 criteria provided, single submitter clinical testing Variant summary: NOTCH1 c.3190G>A (p.Asp1064Asn) results in a conservative amino acid change located in the EGF-like domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 248542 control chromosomes. To our knowledge, no occurrence of c.3190G>A in individuals affected with Adams-Oliver Syndrome 5 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001797107 SCV002011596 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
GeneDx RCV001797107 SCV002038644 uncertain significance not provided 2025-04-15 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this missense variant does not alter protein structure/function
Ambry Genetics RCV004822110 SCV005456606 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-07-31 criteria provided, single submitter clinical testing The p.D1064N variant (also known as c.3190G>A), located in coding exon 20 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 3190. The aspartic acid at codon 1064 is replaced by asparagine, an amino acid with highly similar properties. This variant has been detected in an individual with hypoplastic left heart (Stanley KJ et al. Eur J Hum Genet. 2024 Jul;32(7):795-803). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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