ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1559A>G (p.His520Arg)

dbSNP: rs1220672669
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001049558 SCV001213614 uncertain significance Tuberous sclerosis 2 2020-11-22 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TSC2-related conditions. This sequence change replaces histidine with arginine at codon 520 of the TSC2 protein (p.His520Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine.
Ambry Genetics RCV002400279 SCV002704402 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-31 criteria provided, single submitter clinical testing The p.H520R variant (also known as c.1559A>G), located in coding exon 14 of the TSC2 gene, results from an A to G substitution at nucleotide position 1559. The histidine at codon 520 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003467760 SCV004204526 uncertain significance Isolated focal cortical dysplasia type II 2023-10-18 criteria provided, single submitter clinical testing

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