ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2072G>T (p.Arg691Leu)

gnomAD frequency: 0.00003  dbSNP: rs370553131
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189994 SCV000243666 uncertain significance not provided 2022-10-28 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: 31925297)
Labcorp Genetics (formerly Invitae), Labcorp RCV001083287 SCV000544496 benign Tuberous sclerosis 2 2024-10-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV001014296 SCV001174990 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-20 criteria provided, single submitter clinical testing The p.R691L variant (also known as c.2072G>T), located in coding exon 18 of the TSC2 gene, results from a G to T substitution at nucleotide position 2072. The arginine at codon 691 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV001083287 SCV002039616 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996887 SCV004817465 uncertain significance Tuberous sclerosis syndrome 2023-03-04 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 691 of the TSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 complex in the literature. This variant has been identified in 3/239524 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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