Total submissions: 5
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- |
RCV000822729 | SCV002553401 | uncertain significance | Adams-Oliver syndrome 5 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Genome- |
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, |
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. |