Submissions for variant NM_000548.5(TSC2):c.2927G>C (p.Arg976Pro)

dbSNP: rs779832805

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001230672	SCV001403160	benign	Tuberous sclerosis 2	2023-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001773522	SCV001993421	uncertain significance	not provided	2020-04-10	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
Genome-Nilou Lab	RCV001230672	SCV002040734	uncertain significance	Tuberous sclerosis 2	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436898	SCV002748758	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-28	criteria provided, single submitter	clinical testing	The p.R976P variant (also known as c.2927G>C), located in coding exon 25 of the TSC2 gene, results from a G to C substitution at nucleotide position 2927. The arginine at codon 976 is replaced by proline, an amino acid with dissimilar 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.
Fulgent Genetics, Fulgent Genetics	RCV002484259	SCV002783537	uncertain significance	Lymphangiomyomatosis; Isolated focal cortical dysplasia type II; Tuberous sclerosis 2	2022-04-08	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004004836	SCV004814978	uncertain significance	Tuberous sclerosis syndrome	2023-06-26	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with proline at codon 976 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 complex in the literature. This variant has been identified in 1/250650 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.