Submissions for variant NM_000548.5(TSC2):c.861G>C (p.Glu287Asp)

gnomAD frequency: 0.00004  dbSNP: rs192567788

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000231494	SCV000285481	benign	Tuberous sclerosis 2	2024-01-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000608375	SCV000730867	likely benign	not specified	2018-01-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV001018094	SCV001179280	likely benign	Hereditary cancer-predisposing syndrome	2020-08-25	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-Nilou Lab	RCV000231494	SCV002041273	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV001018094	SCV002534119	likely benign	Hereditary cancer-predisposing syndrome	2022-01-06	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002500763	SCV002810845	likely benign	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2022-01-05	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002500763	SCV003920602	likely benign	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2022-09-28	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.03% (5/15288) (https://gnomad.broadinstitute.org/variant/16-2058759-G-C?dataset=gnomad_r3). This variant is present in ClinVar, with several labs classifying this variant as Likely Benign or Benign (Variation ID:238095). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000608375	SCV003922737	uncertain significance	not specified	2023-03-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003897530	SCV004710216	likely benign	TSC2-related condition	2021-12-02	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).