ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4313G>A (p.Arg1438Gln)

gnomAD frequency: 0.00001  dbSNP: rs45448791
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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 RCV000543604 SCV000644523 benign Tuberous sclerosis 2 2023-10-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV001022275 SCV001183990 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-19 criteria provided, single submitter clinical testing The p.R1438Q variant (also known as c.4313G>A), located in coding exon 33 of the TSC2 gene, results from a G to A substitution at nucleotide position 4313. The arginine at codon 1438 is replaced by glutamine, an amino acid with highly similar properties. This variant was reportedly de novo in an individual with tuberous sclerosis (Roberts PS et al. J. Med. Genet., 2004 May;41:e69). This amino acid position is poorly 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 RCV000543604 SCV002040822 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000043391 SCV004842951 uncertain significance Tuberous sclerosis syndrome 2023-11-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004700316 SCV005203387 uncertain significance not specified 2024-07-19 criteria provided, single submitter clinical testing Variant summary: TSC2 c.4313G>A (p.Arg1438Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.9e-06 in 1609372 control chromosomes, predominantly at a frequency of 2.2e-05 within the East Asian subpopulation in the gnomAD database v4. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4313G>A has been reported in the literature in four individuals affected with Tuberous Sclerosis Complex, including one occurrence of arising de novo (Roberts_2004, Sudarshan_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15121797, 34849272). ClinVar contains an entry for this variant (Variation ID: 50124). Based on the evidence outlined above, the variant was classified as uncertain significance.
Tuberous sclerosis database (TSC2) RCV000043391 SCV000067197 not provided Tuberous sclerosis syndrome no assertion provided curation

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