Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130758 | SCV000185649 | benign | Hereditary cancer-predisposing syndrome | 2018-12-18 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Gene |
RCV001703939 | SCV000243626 | benign | not provided | 2019-03-19 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 21407264, 23514105, 22558107, 21624971, 24728327, 28873162, 29801666) |
Laboratory for Molecular Medicine, |
RCV000122217 | SCV000270956 | likely benign | not specified | 2020-07-01 | criteria provided, single submitter | clinical testing | The c.275A>T variant in TSC2 has been reported in individuals with Tuberous Sclerosis Complex (Dunlop 2011 PMID: 21407264, Bullich 2018 PMID: 29801666); however, it has also been identified in 0.17% (189/109664) of Finnish chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 50116). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. This variant is classified as Likely Benign due to its frequency in the general population. ACMG/AMP Criteria applied: BS1, BP4. |
Invitae | RCV000989412 | SCV000285313 | benign | Tuberous sclerosis 2 | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000122217 | SCV000305186 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000043383 | SCV000395556 | benign | Tuberous sclerosis syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Eurofins Ntd Llc |
RCV000122217 | SCV000703518 | benign | not specified | 2016-12-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000989412 | SCV001139734 | likely benign | Tuberous sclerosis 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000122217 | SCV001338115 | likely benign | not specified | 2020-01-27 | criteria provided, single submitter | clinical testing | Variant summary: TSC2 c.275A>T (p.Glu92Val) results in a non-conservative amino acid change located in the N-terminal 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 0.001 in 213250 control chromosomes (gnomAD). The observed variant frequency is approximately 14.6- fold 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 benign. c.275A>T has been reported in the literature in individuals affected with Tuberous Sclerosis Complex (examples-Dunlop_2011, Bullich_2018) and in at least one unaffected family member (Dunlop_2011). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Dunlop_2011). Seven ClinVar submitters (evaluation after 2014) classified the variant as benign (n=2)/likely benign (n=5). Based on the evidence outlined above, the variant was classified as likely benign. |
ARUP Laboratories, |
RCV001703939 | SCV001477594 | likely benign | not provided | 2023-11-07 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000989412 | SCV002041202 | benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000130758 | SCV002533326 | benign | Hereditary cancer-predisposing syndrome | 2020-09-21 | criteria provided, single submitter | curation | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001703939 | SCV002774072 | benign | not provided | 2019-03-14 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002477140 | SCV002801178 | likely benign | Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2 | 2022-04-09 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001703939 | SCV003917448 | benign | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | TSC2: BP4, BS1, BS2 |
KCCC/NGS Laboratory, |
RCV000989412 | SCV004016162 | benign | Tuberous sclerosis 2 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000989412 | SCV004360844 | benign | Tuberous sclerosis 2 | 2022-08-10 | criteria provided, single submitter | clinical testing | |
Tuberous sclerosis database |
RCV000043383 | SCV000067189 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation | ||
ITMI | RCV000122217 | SCV000086438 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |