ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.2897A>G (p.Tyr966Cys)

gnomAD frequency: 0.00001  dbSNP: rs762213436
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002030186 SCV002109186 uncertain significance Tuberous sclerosis 1 2021-07-03 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with TSC1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is present in population databases (rs762213436, ExAC 0.003%). This sequence change replaces tyrosine with cysteine at codon 966 of the TSC1 protein (p.Tyr966Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine.
Fulgent Genetics, Fulgent Genetics RCV002506872 SCV002816275 uncertain significance Lymphangiomyomatosis; Tuberous sclerosis 1; Isolated focal cortical dysplasia type II 2021-09-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV003164015 SCV003911751 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-22 criteria provided, single submitter clinical testing The c.2897A>G (p.Y966C) alteration is located in exon 22 (coding exon 20) of the TSC1 gene. This alteration results from a A to G substitution at nucleotide position 2897, causing the tyrosine (Y) at amino acid position 966 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003442920 SCV004169183 uncertain significance not provided 2023-11-06 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18466115)

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