ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5177A>C (p.His1726Pro)

dbSNP: rs1555440475
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000549406 SCV000644612 uncertain significance Tuberous sclerosis 2 2023-09-12 criteria provided, single submitter clinical testing 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. This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1726 of the TSC2 protein (p.His1726Pro). 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: 468144). 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.
Ambry Genetics RCV000573694 SCV000675578 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-22 criteria provided, single submitter clinical testing The p.H1726P variant (also known as c.5177A>C), located in coding exon 40 of the TSC2 gene, results from an A to C substitution at nucleotide position 5177. The histidine at codon 1726 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000549406 SCV002040878 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003419962 SCV004115751 uncertain significance TSC2-related condition 2022-11-03 criteria provided, single submitter clinical testing The TSC2 c.5177A>C variant is predicted to result in the amino acid substitution p.His1726Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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