ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5383C>T (p.Arg1795Cys) (rs45517423)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000034665 SCV000884758 likely benign not provided 2017-08-09 criteria provided, single submitter clinical testing The TSC2 c.5383C>T;p.Arg1795Cys variant (also called R1772C by traditional nomenclature) has been described in the medical literature in an individual with a diagnosis of tuberous sclerosis complex who also carried a likely pathogenic in-frame deletion (Nellist 2008). The variant has also been described as occurring at a higher frequency in a reportedly unaffected population than is expected for the disorder (Olfson 2015). The variant is listed in the ClinVar database (Variation ID: 41748) as benign or likely benign. The variant is listed in the dbSNP variant database (rs45517423) with an allele frequency of 0.1309 percent (17/12971 alleles) in the Exome Variant Server and 0.1427 percent (390/273322 alleles, 1 homozygote) in the Genome Aggregation Database. The amino acid at this position is well conserved across species and computational algorithms (Polyphen2, SIFT) predict this variant is deleterious. However, in at least one functional assay, this variant was shown to behave as wild-type (Hoogeveen-Westerveld 2011). Considering available information, this variant is classified as likely benign. References: Hoogeveen-Westerveld M et al. Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex. Hum Mutat. 2011 Apr;32(4):424-35. Nellist M et al. Functional characterisation of the TSC1-TSC2 complex to assess multiple TSC2 variants identified in single families affected by tuberous sclerosis complex. BMC Med Genet. 2008 Feb 26;9:10. Olfson E et al. Identification of Medically Actionable Secondary Findings in the 1000 Genomes. PLoS One. 2015 Sep 2;10(9):e0135193.
Ambry Genetics RCV000163344 SCV000213878 likely benign Hereditary cancer-predisposing syndrome 2018-03-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Intact protein function observed in appropriate functional assay(s),Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Athena Diagnostics Inc RCV000034665 SCV000844592 benign not provided 2017-12-04 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034665 SCV000043548 probably not pathogenic not provided 2012-07-13 no assertion criteria provided research Converted during submission to Likely benign.
CSER_CC_NCGL; University of Washington Medical Center RCV000148917 SCV000190670 uncertain significance Tuberous sclerosis and lymphangiomyomatosis 2014-06-01 no assertion criteria provided research
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034665 SCV000511761 likely benign not provided 2016-11-30 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178483 SCV000230568 likely benign not specified 2014-07-15 criteria provided, single submitter clinical testing
GeneDx RCV000178483 SCV000243618 benign not specified 2014-08-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago RCV000178483 SCV000249208 uncertain significance not specified 2015-06-23 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000054862 SCV000395686 likely benign Tuberous sclerosis syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000204788 SCV000261971 benign Tuberous sclerosis 2 2018-01-12 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000178483 SCV000540604 likely benign not specified 2017-01-24 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is classified in HGMD as DM and seen in 7 papers, including in patients who inherited the mutation from unaffected parents. This variant is present in gnomAD with a Max MAF of 0.36% of Ashkenazi Jews (36/10110 chrs and homozygous in 1 Latino). High for tuberous sclerosis incidence of 1/25000-1/11300. The variant is classified with 1 star in ClinVar as VUS by 3 submitters (CSER_CC_NCGL, University of Chicago, and Ambry), Likely benign by 3 submitters (Emory, Invitae, Biesecker), and Benign by GeneDx.
Tuberous sclerosis database (TSC2) RCV000054862 SCV000067067 not provided Tuberous sclerosis syndrome no assertion provided curation
Tuberous sclerosis database (TSC2) RCV000055245 SCV000083464 not provided Lymphangiomyomatosis; Tuberous sclerosis syndrome no assertion provided curation

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