Submissions for variant NM_001370259.2(MEN1):c.61C>A (p.Arg21Ser)

dbSNP: rs541476418

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000396094	SCV000373106	uncertain significance	Hyperparathyroidism	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000864930	SCV000373107	benign	Multiple endocrine neoplasia, type 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.
Ambry Genetics	RCV000563926	SCV000673620	benign	Hereditary cancer-predisposing syndrome	2023-11-15	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	RCV000864930	SCV001005817	likely benign	Multiple endocrine neoplasia, type 1	2025-01-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001770241	SCV001994234	uncertain significance	not provided	2024-03-21	criteria provided, single submitter	clinical testing	Observed in a patient with a duodenopancreatic neuroendocrine tumor and hyperparathyroidism, co-occurring with a pathogenic MEN1 variant (PMID: 30339208); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29641532, 9989505, 30339208)
Revvity Omics, Revvity	RCV000864930	SCV003808782	uncertain significance	Multiple endocrine neoplasia, type 1	2023-11-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586674	SCV005077138	likely benign	not specified	2024-04-20	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000864930	SCV005403618	likely benign	Multiple endocrine neoplasia, type 1	2024-08-06	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.