ClinVar Miner

Submissions for variant NM_000548.3(TSC2):c.5116C>T (p.Arg1706Cys) (rs45517391)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571102 SCV000675489 likely benign Hereditary cancer-predisposing syndrome 2017-12-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,Intact protein function observed in appropriate functional assay(s)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512881 SCV000608741 uncertain significance not provided 2017-04-30 criteria provided, single submitter clinical testing
GeneDx RCV000189943 SCV000243610 benign not specified 2016-06-08 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.
Illumina Clinical Services Laboratory,Illumina RCV000043179 SCV000395675 likely benign Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000189943 SCV000918329 likely benign not specified 2018-03-17 criteria provided, single submitter clinical testing Variant summary: TSC2 c.5116C>T (p.Arg1706Cys) results in a non-conservative amino acid change located in the Rap GTPase activating protein domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The observed variant frequency is approximately 4-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. The variant, c.5116C>T, has been reported in the literature in individuals affected with Tuberous Sclerosis Complex (Jozwiak_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Tuberous Sclerosis Complex. A functional study, Hoogeveen-Westerveld_2012, found the variant to act comparable to wild type protein and classified as probably neutral. An internal specimen reports the variant to co-occur with pathogenic FLCN, c.927_954dup28. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000229384 SCV000285440 benign Tuberous sclerosis 2 2017-12-15 criteria provided, single submitter clinical testing
Tuberous sclerosis database (TSC2) RCV000043179 SCV000066979 not provided Tuberous sclerosis syndrome no assertion provided curation

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