ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2087G>A (p.Cys696Tyr) (rs45486196)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490930 SCV000579606 likely pathogenic Hereditary cancer-predisposing syndrome 2016-09-12 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Deficient protein function in appropriate functional assay(s)
Invitae RCV001240824 SCV001413800 likely pathogenic Tuberous sclerosis 2 2019-10-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 696 of the TSC2 protein (p.Cys696Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with tuberous sclerosis (PMID: 10205261, Invitae). ClinVar contains an entry for this variant (Variation ID: 50106). This variant has been reported to affect TSC2 protein function (PMID: 10205261, 15483652, 21309039). This variant disrupts the p.Cys696 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been observed in individuals with TSC2-related conditions (PMID: 16981987), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Tuberous sclerosis database (TSC2) RCV000043373 SCV000067179 not provided Tuberous sclerosis syndrome no assertion provided curation

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