ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3986G>A (p.Arg1329His) (rs45517323)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163277 SCV000213805 benign Hereditary cancer-predisposing syndrome 2014-12-01 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000118707 SCV000229649 benign not specified 2015-04-21 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034655 SCV000280858 likely benign not provided 2015-08-19 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
PreventionGenetics,PreventionGenetics RCV000118707 SCV000305212 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000054856 SCV000395640 likely benign Tuberous sclerosis syndrome 2017-04-27 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000462108 SCV000556600 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000118707 SCV000605461 benign not specified 2018-12-19 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000462108 SCV000677546 benign Tuberous sclerosis 2 2017-05-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000034655 SCV000697468 benign not provided 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The TSC2 c.3986G>A (p.Arg1329His) variant causes a missense change involving a non-conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a "damaging" outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 708/97938 (11 homozygotes, 1/138), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TSC2 variant of 1/14534, suggesting this is likely a benign polymorphism. In addition, multiple reputable clinical laboratories/databases cite the variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign.
SIB Swiss Institute of Bioinformatics RCV000462108 SCV000803521 benign Tuberous sclerosis 2 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Benign - Stand Alone, for Tuberous sclerosis 2, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project and 1000 Genomes Project, or Exome Aggregation Consortium.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034655 SCV000043538 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
Tuberous sclerosis database (TSC2) RCV000054856 SCV000066332 not provided Tuberous sclerosis syndrome no assertion provided curation
ITMI RCV000118707 SCV000086453 not provided not specified 2013-09-19 no assertion provided reference population
Genetic Services Laboratory,University of Chicago RCV000118707 SCV000153122 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

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