ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.3408T>A (p.Asp1136Glu)

gnomAD frequency: 0.00001  dbSNP: rs751398082
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164106 SCV000214720 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-07 criteria provided, single submitter clinical testing The p.D1136E variant (also known as c.3408T>A), located in coding exon 21 of the TSC1 gene, results from a T to A substitution at nucleotide position 3408. The aspartic acid at codon 1136 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration, designated as c.3408A>T, was identified in a cohort of individuals with nonsyndromic keratoconus undergoing TSC1 gene testing by whole-exome sequencing (Bykhovskaya Y et al. Invest. Ophthalmol. Vis. Sci. 2017 12;58:6462-6469). This amino acid position is not well conserved in available vertebrate species. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000463228 SCV000552338 benign Tuberous sclerosis 1 2023-12-13 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000463228 SCV002039993 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003474851 SCV004204428 uncertain significance Isolated focal cortical dysplasia type II 2023-10-10 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003995315 SCV004840442 uncertain significance Tuberous sclerosis syndrome 2023-10-27 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 1136 of the TSC1 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 been reported in individuals affected with nonsyndromic keratoconus in the literature (PMID: 29261847). 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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