Submissions for variant NM_000548.5(TSC2):c.251C>T (p.Ala84Val)

gnomAD frequency: 0.00019  dbSNP: rs35660529

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000589638	SCV000243624	benign	not provided	2019-11-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11208653, 28873162, 23514105)
Invitae	RCV001084150	SCV000285296	benign	Tuberous sclerosis 2	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000575144	SCV000675481	likely benign	Hereditary cancer-predisposing syndrome	2018-11-14	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589638	SCV000697463	benign	not provided	2016-08-23	criteria provided, single submitter	clinical testing	Variant summary: The TSC2 c.251C>T (p.Ala84Val) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 20/32398 control chromosomes, predominantly observed in the European (Non-Finnish) and South Asian subpopulations at a frequency of 0.0008709 (14/16076) and 0.000704 (6/8528), respectively. This frequencies is about 10-13 times the estimated maximal expected allele frequency of a pathogenic TSC2 variant (0.0000688), suggesting this is likely a benign polymorphism found primarily in these two subpopulations. Co-occurrence of the variant of interest and a potential pathogenic TSC1 variant (c.1112T>G/p.Tyr297X) has been reported in one TSC patient. In addition, multiple clinical diagnostic laboratories classified this variant as likely benign. Taken together, this variant is classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000589638	SCV000892152	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	TSC2: BP4
Illumina Laboratory Services, Illumina	RCV000042470	SCV001277180	uncertain significance	Tuberous sclerosis syndrome	2018-07-10	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001084150	SCV002041046	benign	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000575144	SCV002531076	benign	Hereditary cancer-predisposing syndrome	2021-02-13	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001084150	SCV004016141	benign	Tuberous sclerosis 2	2023-07-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589638	SCV004221420	benign	not provided	2011-02-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001084150	SCV004360841	likely benign	Tuberous sclerosis 2	2022-08-31	criteria provided, single submitter	clinical testing
Tuberous sclerosis database (TSC2)	RCV000042470	SCV000066261	not provided	Tuberous sclerosis syndrome		no assertion provided	curation
Tuberous sclerosis database (TSC2)	RCV000055051	SCV000083269	not provided	Lymphangiomyomatosis; Tuberous sclerosis syndrome		no assertion provided	curation
Clinical Genetics, Academic Medical Center	RCV000589638	SCV001978855	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001729369	SCV001980212	benign	not specified		no assertion criteria provided	clinical testing