Submissions for variant NM_020975.6(RET):c.833C>A (p.Thr278Asn)

gnomAD frequency: 0.00056  dbSNP: rs35118262

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163444	SCV000213991	benign	Hereditary cancer-predisposing syndrome	2017-06-27	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083124	SCV000261217	benign	Multiple endocrine neoplasia, type 2	2024-02-01	criteria provided, single submitter	clinical testing
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000490442	SCV000267474	likely benign	Hirschsprung disease, susceptibility to, 1	2016-03-18	criteria provided, single submitter	reference population
Illumina Laboratory Services, Illumina	RCV000490442	SCV000362270	benign	Hirschsprung disease, susceptibility to, 1	2018-03-06	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000121990	SCV000540167	likely benign	not specified	2016-04-25	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: 2.7% East Asian population ExAC, LB by Ambry 2014
GeneDx	RCV000034778	SCV000729739	benign	not provided	2020-04-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24845513, 24728327, 17009072, 20981092, 26152202, 21251878, 25122427, 22703879, 24618965, 22174939, 22640420, 19443294, 27153395, 26332594, 22377709, 29192238, 28775167, 31180159)
PreventionGenetics, part of Exact Sciences	RCV000121990	SCV000807061	benign	not specified	2017-10-13	criteria provided, single submitter	clinical testing
Mendelics	RCV000988341	SCV001138021	benign	Multiple endocrine neoplasia type 2A	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001104178	SCV001261021	benign	Pheochromocytoma	2018-03-06	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 Laboratory Services, Illumina	RCV001104179	SCV001261022	likely benign	Renal hypodysplasia/aplasia 1	2018-03-06	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 Laboratory Services, Illumina	RCV001104180	SCV001261023	benign	Multiple endocrine neoplasia	2018-03-06	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.
Sema4, Sema4	RCV000163444	SCV002527928	benign	Hereditary cancer-predisposing syndrome	2021-05-18	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000034778	SCV004127589	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	RET: BP4, BS1, BS2
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000121990	SCV004220048	benign	not specified	2022-08-28	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. Computational tools predict this amino acid change may be benign.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121990	SCV004243364	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001083124	SCV004357223	benign	Multiple endocrine neoplasia, type 2	2022-09-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034778	SCV004564906	benign	not provided	2023-05-25	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034778	SCV000043471	variant of unknown significance	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Uncertain significance.
ITMI	RCV000121990	SCV000086201	not provided	not specified	2013-09-19	no assertion provided	reference population