Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000190042 | SCV000243716 | uncertain significance | not provided | 2017-10-26 | criteria provided, single submitter | clinical testing | This variant is denoted TSC2 c.5252G>A at the cDNA level, p.Arg1751His (R1751H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. TSC2 Arg1751His was observed at an allele frequency of 0.01% (1/10,068 alleles) in large population cohorts (Lek 2016). This variant is located in the Rap-GAP domain (UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether TSC2 Arg1751His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV001084515 | SCV000544472 | benign | Tuberous sclerosis 2 | 2024-01-17 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001084515 | SCV002040266 | likely benign | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV002257483 | SCV002534039 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-26 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002257483 | SCV002643810 | likely benign | Hereditary cancer-predisposing syndrome | 2021-09-10 | 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. |
Laboratory of Molecular Epidemiology of Birth Defects, |
RCV003153466 | SCV003843663 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003895237 | SCV004710604 | uncertain significance | TSC2-related condition | 2024-02-12 | criteria provided, single submitter | clinical testing | The TSC2 c.5252G>A variant is predicted to result in the amino acid substitution p.Arg1751His. This variant was reported in an individual with breast cancer (Table S2, McDonald et al. 2022. PubMed ID: 36315513). This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD and has conflicting interpretations of pathogenicity in ClinVar ranging from benign to likely pathogenic (http://www.ncbi.nlm.nih.gov/clinvar/variation/207760). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |