ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3915G>A (p.Pro1305=) (rs11551373)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000118706 SCV000169144 benign not specified 2012-05-24 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 RCV000129645 SCV000184440 benign Hereditary cancer-predisposing syndrome 2014-11-30 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 RCV000118706 SCV000269920 benign not specified 2013-02-21 criteria provided, single submitter clinical testing Pro1305Pro in exon 33 of TSC2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 6.6% (290/4372) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs11551373).
PreventionGenetics,PreventionGenetics RCV000118706 SCV000305211 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000042539 SCV000395638 benign Tuberous sclerosis syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000470595 SCV000556687 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000470595 SCV000677545 benign Tuberous sclerosis 2 2017-05-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587118 SCV000697467 benign not provided 2016-08-23 criteria provided, single submitter clinical testing Variant summary: The TSC2 c.3915G>A (p.Pro1305Pro) variant causes a synonymous change involving a non-conserved nucleotide with 4/5 splice prediction tools predicting no significant impact on splicing or ESE binding, 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 536/51912 (14 homozygotes, 1/96), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TSC2 variant of 1/14534 (0.0000688), suggesting this variant is likely a benign polymorphism. In addition, multiple reputable clinical laboratories/databases cite the variant as "benign/likely benign." Therefore, the variant of interest has been classified as Benign.
Tuberous sclerosis database (TSC2) RCV000042539 SCV000066331 not provided Tuberous sclerosis syndrome no assertion provided curation
Genetic Services Laboratory,University of Chicago RCV000118706 SCV000153121 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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