ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.170G>A (p.Arg57His)

gnomAD frequency: 0.00001  dbSNP: rs397514949
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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 RCV000472366 SCV000544328 benign Tuberous sclerosis 2 2024-10-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002399416 SCV002712265 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-23 criteria provided, single submitter clinical testing The p.R57H variant (also known as c.170G>A), located in coding exon 2 of the TSC2 gene, results from a G to A substitution at nucleotide position 170. The arginine at codon 57 is replaced by histidine, an amino acid with highly similar properties. Functional analysis of this alteration a TSC1 binding signal similar to wildtype; a slightly decreased TSC2 signal, suggesting instability; and a significantly increased phospho-S6K signal (Hoogeveen-Westerveld M et al. Hum. Mutat., 2011 Apr;32:424-35). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Athena Diagnostics RCV003482235 SCV004229359 uncertain significance not provided 2023-01-24 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 21309039) The variant is located in a region that is considered important for protein function and/or structure. Computational tools predict that this variant is damaging.
Tuberous sclerosis database (TSC2) RCV000055135 SCV000083353 not provided Tuberous sclerosis syndrome no assertion provided curation

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