ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1336G>C (p.Gly446Arg) (rs115423919)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083435 SCV000166601 benign Multiple endocrine neoplasia, type 2 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162955 SCV000213443 benign Hereditary cancer-predisposing syndrome 2014-12-23 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000121994 SCV000232293 benign not specified 2015-02-20 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000121994 SCV000313713 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000317413 SCV000362299 benign Hirschsprung disease 1 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000372019 SCV000362300 benign Pheochromocytoma 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000282253 SCV000362301 likely benign Renal hypodysplasia/aplasia 1 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.
Illumina Clinical Services Laboratory,Illumina RCV000337299 SCV000362302 benign Multiple endocrine neoplasia 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Counsyl RCV000411174 SCV000489771 likely benign Multiple endocrine neoplasia, type 2b 2015-12-22 criteria provided, single submitter clinical testing
Counsyl RCV000409372 SCV000489772 likely benign Multiple endocrine neoplasia, type 2a 2015-12-22 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000121994 SCV000711344 likely benign not specified 2016-12-14 criteria provided, single submitter clinical testing p.Gly446Arg in exon 7 of RET: This variant is not expected to have clinical sign ificance because it has been identified in 0.8% (87/10400) of African chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs115423919).
GeneDx RCV000121994 SCV000716910 likely benign not specified 2017-10-03 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.
Athena Diagnostics Inc RCV000712293 SCV000842749 benign not provided 2018-05-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000121994 SCV001338394 benign not specified 2020-02-26 criteria provided, single submitter clinical testing Variant summary: RET c.1336G>C (p.Gly446Arg) results in a non-conservative amino acid change located in the RET cadherin-like domain 4 (IPR041317) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0008 in 282840 control chromosomes, predominantly at a frequency of 0.0083 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 200 fold of the estimated maximal expected allele frequency for a pathogenic variant in RET causing Multiple Endocrine Neoplasia Type 2 phenotype (3.7e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all of them classified the variant as benign (4x) / likely benign (4x). Based on the evidence outlined above, the variant was classified as benign.
ITMI RCV000121994 SCV000086205 not provided not specified 2013-09-19 no assertion provided reference population

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.