ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3914C>T (p.Pro1305Leu) (rs45517320)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118705 SCV000169143 benign not specified 2012-05-11 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 RCV000130814 SCV000185710 benign Hereditary cancer-predisposing syndrome 2014-12-22 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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000118705 SCV000205288 benign not specified 2013-02-21 criteria provided, single submitter clinical testing Pro1305Leu in exon 33 of TSC2: This variant is not expected to have clinical sig nificance because it has been identified in 2.1% (91/4368) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /; dbSNP rs45517320).
Vantari Genetics RCV000130814 SCV000267098 likely benign Hereditary cancer-predisposing syndrome 2016-02-04 criteria provided, single submitter clinical testing
Invitae RCV000234232 SCV000285373 benign Tuberous sclerosis 2 2020-12-07 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000118705 SCV000305210 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000054866 SCV000395637 likely benign Tuberous sclerosis syndrome 2018-02-09 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.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034654 SCV000610914 likely benign not provided 2017-06-12 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000234232 SCV000677544 benign Tuberous sclerosis 2 2017-05-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000034654 SCV000697466 benign not provided 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The TSC2 c.3914C>T (p.Pro1305Leu) variant causes a missense change involving a non-conserved nucleotide. 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a benign 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 232/49978 (5 homozygotes, 1/250), predominantly in the African cohort, 220/5384 (1/24), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TSC2 variant of 1/14534 (0.0000688). Therefore, suggesting the variant is a common benign polymorphism found in population(s) of African origin. In addition, multiple reputable clinical laboratories/databases cite the variant as "likely benign/benign." Therefore, the variant of interest has been classified as Benign.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034654 SCV000043537 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
Tuberous sclerosis database (TSC2) RCV000054866 SCV000066330 not provided Tuberous sclerosis syndrome no assertion provided curation
ITMI RCV000118705 SCV000086450 not provided not specified 2013-09-19 no assertion provided reference population
Genetic Services Laboratory, University of Chicago RCV000118705 SCV000153120 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000118705 SCV001808283 benign not specified no assertion criteria provided clinical testing

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