ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1378G>A (p.Ala460Thr)

gnomAD frequency: 0.00035  dbSNP: rs137854154
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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130880 SCV000185785 benign Hereditary cancer-predisposing syndrome 2015-08-20 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Co-occurence with mutation in same gene (phase unknown);General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Other data supporting benign classification
Invitae RCV000989417 SCV000261891 benign Tuberous sclerosis 2 2021-12-18 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000122206 SCV000336111 likely benign not specified 2015-10-21 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000042922 SCV000395580 likely benign Tuberous sclerosis syndrome 2018-02-12 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000122206 SCV000540600 benign not specified 2016-04-25 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.5% (46/8536) European chromosomes; ClinVar: 2 labs classify as LB. 3/5 pubs describe as nonpathogenic.
Mendelics RCV000989417 SCV001139739 likely benign Tuberous sclerosis 2 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000204918 SCV001150690 likely benign not provided 2022-04-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000122206 SCV001748775 benign not specified 2021-06-28 criteria provided, single submitter clinical testing Variant summary: TSC2 c.1378G>A (p.Ala460Thr) results in a non-conservative amino acid change located in the Tuberin, N-terminal domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 155816 control chromosomes in the gnomAD database, including 2 homozygotes. The observed variant frequency is approximately 18.11 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 benign. To our knowledge, no occurrence of c.1378G>A in individuals affected with Tuberous Sclerosis Complex and no experimental evidence demonstrating its impact on protein function have been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000204918 SCV001940283 benign not provided 2018-11-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25281918, 25637381, 21309039, 24728327, 19258292, 27884173)
Genome-Nilou Lab RCV000989417 SCV002041333 benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000122206 SCV002069942 likely benign not specified 2021-10-07 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000130880 SCV002532780 benign Hereditary cancer-predisposing syndrome 2020-05-10 criteria provided, single submitter curation
Tuberous sclerosis database (TSC2) RCV000042922 SCV000066719 not provided Tuberous sclerosis syndrome no assertion provided curation
ITMI RCV000122206 SCV000086427 not provided not specified 2013-09-19 no assertion provided reference population
CSER _CC_NCGL, University of Washington RCV000042922 SCV000190665 likely benign Tuberous sclerosis syndrome 2014-06-01 no assertion criteria provided research
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV000989417 SCV001190850 benign Tuberous sclerosis 2 2020-02-05 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000122206 SCV001808527 benign not specified no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000122206 SCV001925923 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000122206 SCV001975849 benign not specified no assertion criteria provided clinical testing

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