ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4603G>A (p.Asp1535Asn)

gnomAD frequency: 0.00001  dbSNP: rs45517353
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000981686 SCV001129669 likely benign Tuberous sclerosis 2 2024-12-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002337030 SCV002635459 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-27 criteria provided, single submitter clinical testing The p.D1535N variant (also known as c.4603G>A), located in coding exon 35 of the TSC2 gene, results from a G to A substitution at nucleotide position 4603. The aspartic acid at codon 1535 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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.
All of Us Research Program, National Institutes of Health RCV004004399 SCV004824696 uncertain significance Tuberous sclerosis syndrome 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 1535 of the TSC2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 been identified in 3/249986 chromosomes 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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