ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5155G>A (p.Ala1719Thr)

gnomAD frequency: 0.00001  dbSNP: rs201206500
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000468508 SCV000544356 likely benign Tuberous sclerosis 2 2024-08-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000572428 SCV000675680 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-25 criteria provided, single submitter clinical testing The p.A1719T variant (also known as c.5155G>A), located in coding exon 39 of the TSC2 gene, results from a G to A substitution at nucleotide position 5155. The alanine at codon 1719 is replaced by threonine, an amino acid with similar properties. This alteration was identified in a cohort of individuals undergoing exome analysis for sporadic autism spectrum disorders in both the affected child and an unaffected parent (O'Roak BJ et al. Nat. Genet., 2011 Jun;43:585-9). 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.
Genome-Nilou Lab RCV000468508 SCV002040255 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
GeneDx RCV003162430 SCV003915101 uncertain significance not provided 2023-04-10 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21572417, 21819393, 29617669)
All of Us Research Program, National Institutes of Health RCV003996480 SCV004817511 uncertain significance Tuberous sclerosis syndrome 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 1719 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 tuberous sclerosis in the literature, but has been found in unaffected individuals (PMID: 21572417). This variant has been identified in 4/250272 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.
Tuberous sclerosis database (TSC2) RCV000055435 SCV000083656 not provided Autism spectrum disorder no assertion provided curation

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