Submissions for variant NM_020975.6(RET):c.1942G>A (p.Val648Ile)

gnomAD frequency: 0.00007  dbSNP: rs77711105

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CSER _CC_NCGL, University of Washington	RCV000014976	SCV000190518	uncertain significance	Multiple endocrine neoplasia, type 2a	2014-06-01	criteria provided, single submitter	research	Low GERP score may suggest that this variant may belong in a lower pathogenicity class
Ambry Genetics	RCV000163319	SCV000213847	benign	Hereditary cancer-predisposing syndrome	2018-10-11	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Invitae	RCV001082776	SCV000253560	likely benign	Multiple endocrine neoplasia, type 2	2024-01-27	criteria provided, single submitter	clinical testing
Vantari Genetics	RCV000163319	SCV000267089	likely benign	Hereditary cancer-predisposing syndrome	2016-02-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000442648	SCV000521037	likely benign	not specified	2017-09-29	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.
Counsyl	RCV000014976	SCV000785294	uncertain significance	Multiple endocrine neoplasia, type 2a	2017-06-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000034767	SCV000807016	likely benign	not provided	2017-09-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000014976	SCV000838392	likely benign	Multiple endocrine neoplasia, type 2a	2018-07-02	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163319	SCV002529955	likely benign	Hereditary cancer-predisposing syndrome	2021-11-15	criteria provided, single submitter	curation
MGZ Medical Genetics Center	RCV000014976	SCV002579940	uncertain significance	Multiple endocrine neoplasia, type 2a	2022-05-03	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000014976	SCV004018473	likely benign	Multiple endocrine neoplasia, type 2a	2023-04-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
OMIM	RCV000014976	SCV000035232	pathogenic	Multiple endocrine neoplasia, type 2a	2002-12-01	no assertion criteria provided	literature only
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034767	SCV000043473	probably not pathogenic	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Likely benign.