Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000546990 | SCV000644460 | likely benign | Tuberous sclerosis 2 | 2024-01-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000575342 | SCV000664745 | likely benign | Hereditary cancer-predisposing syndrome | 2021-02-06 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Genome- |
RCV000546990 | SCV002041060 | likely benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000575342 | SCV002533434 | likely benign | Hereditary cancer-predisposing syndrome | 2022-02-10 | criteria provided, single submitter | curation | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469054 | SCV002766082 | likely benign | not specified | 2022-11-09 | criteria provided, single submitter | clinical testing | Variant summary: TSC2 c.362C>G (p.Ala121Gly) results in a non-conservative amino acid change located in the Tuberin, N-terminal domain (IPR024584) 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 5.2e-05 in 251468 control chromosomes, predominantly at a frequency of 0.00038 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 5.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in TSC2 causing Tuberous Sclerosis Complex phenotype (6.9e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.362C>G in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported in the literature. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=3) and as uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477648 | SCV004221441 | likely benign | not provided | 2018-01-29 | criteria provided, single submitter | clinical testing |