ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2835C>G (p.Asp945Glu)

gnomAD frequency: 0.00002  dbSNP: rs756174213
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001348439 SCV001542743 likely benign Adams-Oliver syndrome 5 2023-06-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003987844 SCV004803615 uncertain significance not specified 2024-01-22 criteria provided, single submitter clinical testing Variant summary: NOTCH1 c.2835C>G (p.Asp945Glu) results in a conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248774 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2835C>G in individuals affected with Adams-Oliver Syndrome 5 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1044217). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV004651604 SCV005142241 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-04-17 criteria provided, single submitter clinical testing The c.2835C>G (p.D945E) alteration is located in exon 18 (coding exon 18) of the NOTCH1 gene. This alteration results from a C to G substitution at nucleotide position 2835, causing the aspartic acid (D) at amino acid position 945 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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