ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5024C>A (p.Pro1675Gln)

dbSNP: rs45483392
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000644091 SCV000765781 pathogenic Tuberous sclerosis 2 2022-03-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 1675 of the TSC2 protein (p.Pro1675Gln). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro1675 amino acid residue in TSC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9302281, 9463313, 11520734, 12111193, 15024740, 21520333, 22867869). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 expected to disrupt TSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 535873). This missense change has been observed in individual(s) with tuberous sclerosis complex (PMID: 21520333; Invitae). In at least one individual the variant was observed to be de novo.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000984876 SCV001132687 likely pathogenic Tuberous sclerosis syndrome 2019-12-27 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000644091 SCV002041013 likely pathogenic Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing

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