ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4655C>T (p.Ala1552Val)

gnomAD frequency: 0.00001  dbSNP: rs748862853
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822729 SCV000963544 likely benign Adams-Oliver syndrome 5 2023-07-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV000822729 SCV001529086 uncertain significance Adams-Oliver syndrome 5 2018-07-13 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 RCV000822729 SCV002553401 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002271052 SCV002553402 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323736 SCV004029525 uncertain significance not specified 2023-07-31 criteria provided, single submitter clinical testing Variant summary: NOTCH1 c.4655C>T (p.Ala1552Val) results in a non-conservative amino acid change located in the Notch 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 1.7e-05 in 239632 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.4655C>T in individuals affected with Adams-Oliver Syndrome 5 has been reported. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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