ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.556G>A (p.Ala186Thr) (rs1279777367)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558926 SCV000641662 uncertain significance Tuberous sclerosis 1 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 186 of the TSC1 protein (p.Ala186Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TSC1-related disease. This variant has been reported in a single family affected with autism (PMID: 23999528). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000566027 SCV000664726 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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