ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.9592C>T (p.Arg3198Trp)

gnomAD frequency: 0.00511  dbSNP: rs149842139
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000081924 SCV000113859 benign not specified 2013-10-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000081924 SCV000249428 likely benign not specified 2015-06-30 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000710111 SCV000616280 likely benign not provided 2018-03-27 criteria provided, single submitter clinical testing
Invitae RCV000531326 SCV000630897 benign Cohen syndrome 2021-12-18 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000531326 SCV000743197 likely benign Cohen syndrome 2016-11-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000717556 SCV000848409 benign History of neurodevelopmental disorder 2018-07-19 criteria provided, single submitter clinical testing In silico models in agreement (benign) ;Other strong data;Sub-population frequency in support of benign classification (not ava blue, manual h-w)
Fulgent Genetics,Fulgent Genetics RCV000531326 SCV000883057 likely benign Cohen syndrome 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000710111 SCV000892864 likely benign not provided 2022-05-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000531326 SCV001326316 likely benign Cohen 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 RCV000710111 SCV001949031 benign not provided 2020-05-29 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25502226, 29706646)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000081924 SCV002547502 benign not specified 2022-05-04 criteria provided, single submitter clinical testing Variant summary: VPS13B c.9667C>T (p.Arg3223Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0036 in 250822 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 1.44 fold of the estimated maximal expected allele frequency for a pathogenic variant in VPS13B causing Cohen Syndrome phenotype (0.0025), strongly suggesting that the variant is benign. To our knowledge, no penetrant association of c.9667C>T in individuals affected with Cohen Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000531326 SCV000734591 likely benign Cohen syndrome no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000710111 SCV001922535 likely benign not provided no assertion criteria provided clinical testing
Natera, Inc. RCV000531326 SCV002082718 benign Cohen syndrome 2019-10-18 no assertion criteria provided clinical testing

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