ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1202A>C (p.His401Pro)

dbSNP: rs2086691569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001732820 SCV001983519 uncertain significance not specified 2021-09-25 criteria provided, single submitter clinical testing
Baylor Genetics RCV003470882 SCV004206830 uncertain significance Isolated focal cortical dysplasia type II 2023-09-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV004681236 SCV005180975 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-21 criteria provided, single submitter clinical testing The p.H401P variant (also known as c.1202A>C), located in coding exon 11 of the TSC2 gene, results from an A to C substitution at nucleotide position 1202. The histidine at codon 401 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005057556 SCV005700576 uncertain significance Tuberous sclerosis 2 2024-03-27 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 401 of the TSC2 protein (p.His401Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1301335). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function with a negative predictive value of 95%. 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.

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