ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2008C>G (p.Pro670Ala)

dbSNP: rs1338802781
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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 RCV000804961 SCV000944902 uncertain significance Tuberous sclerosis 2 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 670 of the TSC2 protein (p.Pro670Ala). 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: 649915). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Ambry Genetics RCV003166241 SCV003911452 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-01 criteria provided, single submitter clinical testing The p.P670A variant (also known as c.2008C>G), located in coding exon 18 of the TSC2 gene, results from a C to G substitution at nucleotide position 2008. The proline at codon 670 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is conserved. 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 RCV003467408 SCV004206888 uncertain significance Isolated focal cortical dysplasia type II 2023-07-05 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004803236 SCV005427122 uncertain significance Tuberous sclerosis syndrome 2024-04-16 criteria provided, single submitter clinical testing This missense variant replaces proline with alanine at codon 670 of the TSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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