ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5068G>A (p.Asp1690Asn)

dbSNP: rs137854882
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644178 SCV000765868 uncertain significance Tuberous sclerosis 2 2022-10-07 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1690 of the TSC2 protein (p.Asp1690Asn). This variant also falls at the last nucleotide of exon 39, which is part of the consensus splice site for this exon. This variant has not been reported in the literature in individuals affected with TSC2-related conditions. 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 variant disrupts the c.5068G nucleotide in the TSC2 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 9829910; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 535944).
Institute of Human Genetics, University of Leipzig Medical Center RCV000644178 SCV003804683 likely pathogenic Tuberous sclerosis 2 2023-01-04 criteria provided, single submitter clinical testing Criteria applied: PM1, PM5, PM2_SUP, PP3, PP4

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