ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.1099C>T (p.Arg367Trp)

gnomAD frequency: 0.00001  dbSNP: rs757844109
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000993364 SCV001146272 uncertain significance not provided 2019-08-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001319370 SCV001510112 uncertain significance Tuberous sclerosis 2 2024-04-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 367 of the TSC2 protein (p.Arg367Trp). This variant is present in population databases (rs757844109, gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TSC2-related conditions (PMID: 21520333, 34992632). ClinVar contains an entry for this variant (Variation ID: 805693). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000993364 SCV001777308 uncertain significance not provided 2021-01-05 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; Observed in heterozygous state in a clinically unaffected adult relative of an individual referred for genetic testing at GeneDx
Genome-Nilou Lab RCV001319370 SCV002040589 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002445146 SCV002732779 uncertain significance Hereditary cancer-predisposing syndrome 2021-01-11 criteria provided, single submitter clinical testing The p.R367W variant (also known as c.1099C>T), located in coding exon 10 of the TSC2 gene, results from a C to T substitution at nucleotide position 1099. The arginine at codon 367 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is 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.
All of Us Research Program, National Institutes of Health RCV004004421 SCV004839323 uncertain significance Tuberous sclerosis syndrome 2023-12-01 criteria provided, single submitter clinical testing

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