ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.3184C>T (p.Arg1062Trp) (rs118203745)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189827 SCV000243479 likely benign not specified 2017-07-10 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.
Invitae RCV000227692 SCV000284718 benign Tuberous sclerosis 1 2019-12-31 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000227692 SCV000296908 uncertain significance Tuberous sclerosis 1 2015-08-24 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000189827 SCV000540598 uncertain significance not specified 2016-06-16 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: ClinVar: 1 LB; Reported in one proband, functional studies do not support pathogenicity
Ambry Genetics RCV000563572 SCV000675353 likely benign Hereditary cancer-predisposing syndrome 2019-02-22 criteria provided, single submitter clinical testing Intact protein function observed in appropriate functional assay(s);Other data supporting benign classification
Mendelics RCV000227692 SCV001137927 benign Tuberous sclerosis 1 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000189827 SCV001160281 uncertain significance not specified 2019-03-04 criteria provided, single submitter clinical testing The TSC1 c.3184C>T; p.Arg1062Trp variant (rs118203745) is reported in the literature in an individual with tuberous sclerosis (Qin 2010). However, functional assays demonstrate the variant protein behaves similarly to wild type protein (Hoogeveen-Westerveld 2011). This variant is reported with conflicting interpretations in ClinVar (Variation ID: 49015). It is found in the general population with an overall allele frequency of 0.02% (44/282762 alleles) in the Genome Aggregation Database. The arginine at codon 1062 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant may be deleterious. However, due to limited information, the clinical significance of this variant is uncertain at this time. 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. Qin W et al. Ultra deep sequencing detects a low rate of mosaic mutations in tuberous sclerosis complex. Hum Genet. 2010 Mar;127(5):573-82.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001093203 SCV001250063 uncertain significance not provided 2019-12-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001167647 SCV001330167 benign Focal cortical dysplasia type II 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV000227692 SCV001330168 likely benign Tuberous sclerosis 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Tuberous sclerosis database (TSC1) RCV000042266 SCV000066055 not provided Tuberous sclerosis syndrome no assertion provided curation

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