ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5008C>G (p.His1670Asp)

dbSNP: rs1596454994
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001023412 SCV001185281 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-26 criteria provided, single submitter clinical testing The p.H1670D variant (also known as c.5008C>G), located in coding exon 38 of the TSC2 gene, results from a C to G substitution at nucleotide position 5008. The histidine at codon 1670 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003512102 SCV004290825 uncertain significance Tuberous sclerosis 2 2023-06-30 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 1670 of the TSC2 protein (p.His1670Asp). 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: 825367). 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. 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.
All of Us Research Program, National Institutes of Health RCV004004636 SCV004834461 uncertain significance Tuberous sclerosis syndrome 2024-01-11 criteria provided, single submitter clinical testing

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