Submissions for variant NM_020975.6(RET):c.166C>A (p.Leu56Met)

gnomAD frequency: 0.00310  dbSNP: rs145633958

Total submissions: 29

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000121985	SCV000113984	benign	not specified	2014-06-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000163266	SCV000213794	benign	Hereditary cancer-predisposing syndrome	2015-01-27	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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000202649	SCV000258169	benign	Multiple endocrine neoplasia	2015-06-25	criteria provided, single submitter	clinical testing
Invitae	RCV001082759	SCV000261742	benign	Multiple endocrine neoplasia, type 2	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000034766	SCV000514406	likely benign	not provided	2021-03-18	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in a patient with short segment Hirschsprung disease and in a fetus with bilateral renal agenesis and uterine agenesis (Hofstra et al., 2000; Jeanpierre et al., 2011).; This variant is associated with the following publications: (PMID: 26332594, 24442913, 25569433, 26883533, 24055113, 30840779, 22703879, 20473317, 10790203, 24728327, 26572137, 27153395, 25637381, 22995991, 21490379, 26395553, 22648184, 30072953, 31649719)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000121985	SCV000711342	likely benign	not specified	2016-04-20	criteria provided, single submitter	clinical testing	p.Leu56Met in exon 2 of RET: This variant is not expected to have clinical signi ficance because it has been identified in 0.4% (271/66206) of European chromosom es, including 1 homozygote by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs145633958).
PreventionGenetics, part of Exact Sciences	RCV000121985	SCV000807009	benign	not specified	2016-10-10	criteria provided, single submitter	clinical testing
Mendelics	RCV000030402	SCV001138019	benign	Multiple endocrine neoplasia type 2A	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034766	SCV001147859	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	RET: BP4, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034766	SCV001158030	likely benign	not provided	2023-11-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000202649	SCV001266132	benign	Multiple endocrine neoplasia	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 Laboratory Services, Illumina	RCV001108849	SCV001266133	likely benign	Renal hypodysplasia/aplasia 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001108850	SCV001266134	uncertain significance	Pheochromocytoma	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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001108851	SCV001266135	likely benign	Hirschsprung disease, susceptibility to, 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000034766	SCV002011461	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121985	SCV002067079	benign	not specified	2020-08-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163266	SCV002529940	likely benign	Hereditary cancer-predisposing syndrome	2021-05-31	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000121985	SCV002550377	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000034766	SCV002774043	benign	not provided	2017-08-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001082759	SCV004357214	likely benign	Multiple endocrine neoplasia, type 2	2022-06-09	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001082759	SCV004838625	likely benign	Multiple endocrine neoplasia, type 2	2024-02-05	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034766	SCV000043467	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030402	SCV000053071	benign	Multiple endocrine neoplasia type 2A	2012-03-13	no assertion criteria provided	clinical testing
ITMI	RCV000121985	SCV000086196	not provided	not specified	2013-09-19	no assertion provided	reference population
CSER _CC_NCGL, University of Washington	RCV000148768	SCV000190505	likely benign	Aganglionic megacolon	2014-06-01	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000034766	SCV001741811	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000121985	SCV001807872	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000121985	SCV001952151	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000034766	SCV002036410	likely benign	not provided		no assertion criteria provided	clinical testing