ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.3803G>A (p.Arg1268His)

gnomAD frequency: 0.00001  dbSNP: rs200577441
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000231146 SCV000285366 benign Tuberous sclerosis 2 2025-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000566058 SCV000675548 likely benign Hereditary cancer-predisposing syndrome 2022-02-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000055239 SCV000891019 likely benign Tuberous sclerosis syndrome 2021-05-20 criteria provided, single submitter clinical testing The TSC2 c.3803G>A (p.Arg1268His) change has a maximum subpopulation frequency of 0.14% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/16-2131788-G-A?dataset=gnomad_r2_1). This population frequency exceeds the expected prevalence of a pathogenic variant causing tuberous sclerosis complex (BS1). Five of seven in silico tools predict a deleterious effect of this variant on protein function, however functional studies indicate that this variant does not behave significantly different than the wild-type (https://databases.lovd.nl/). Data in the LOVD database indicates that this variant has been identified in an individual with TSC whom also carries a definite TSC-causing variant (BP2). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria: BS1, BP2.
Illumina Laboratory Services, Illumina RCV000055239 SCV001279815 likely benign Tuberous sclerosis syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV001711223 SCV001940393 benign not provided 2020-05-07 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31927531)
Genome-Nilou Lab RCV000231146 SCV002039375 benign Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004703202 SCV004221445 benign not specified 2022-10-28 criteria provided, single submitter clinical testing The frequency of this variant in the general population (http://gnomad.broadinstitute.org) is higher than would generally be expected for pathogenic variants in this gene. This variant has been seen where an alternate explanation for disease was also identified.
Myriad Genetics, Inc. RCV000231146 SCV005406111 likely benign Tuberous sclerosis 2 2024-08-16 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.
Tuberous sclerosis database (TSC2) RCV000055239 SCV000083458 not provided Tuberous sclerosis syndrome no assertion provided curation

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