ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4106G>A (p.Arg1369Gln)

gnomAD frequency: 0.00002  dbSNP: rs587778738
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564577 SCV000675539 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-30 criteria provided, single submitter clinical testing The p.R1369Q variant (also known as c.4106G>A), located in coding exon 33 of the TSC2 gene, results from a G to A substitution at nucleotide position 4106. The arginine at codon 1369 is replaced by glutamine, an amino acid with highly similar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000644340 SCV000766033 benign Tuberous sclerosis 2 2024-01-27 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000644340 SCV002039829 likely benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
New York Genome Center RCV000644340 SCV002097710 uncertain significance Tuberous sclerosis 2 2021-01-08 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000564577 SCV002533503 likely benign Hereditary cancer-predisposing syndrome 2022-02-16 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000644340 SCV005404760 likely benign Tuberous sclerosis 2 2024-08-06 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
ITMI RCV000122232 SCV000086455 not provided not specified 2013-09-19 no assertion provided reference population
PreventionGenetics, part of Exact Sciences RCV004734661 SCV005362733 uncertain significance TSC2-related disorder 2024-04-11 no assertion criteria provided clinical testing The TSC2 c.4106G>A variant is predicted to result in the amino acid substitution p.Arg1369Gln. This variant was reported in an individual with autism spectrum disorder (Table S3, Saskin et al. 2017. PubMed ID: 28250423; g.2074330 hg18 in Table 1, Schaaf et al. 2011. PubMed: 21624971). However, the variant was also reported in a healthy control (g.2134329 hg19 in Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.011% of alleles in individuals of East Asian descent in gnomAD and has conflicting interpretations ranging from uncertain to benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/135386/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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