Submissions for variant NM_000208.4(INSR):c.3034G>A (p.Val1012Met)

gnomAD frequency: 0.00500  dbSNP: rs1799816

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000175131	SCV000151454	uncertain significance	not specified	2014-07-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000175131	SCV000226563	benign	not specified	2015-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000344820	SCV000415459	benign	Insulin-resistant diabetes mellitus AND acanthosis nigricans	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.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV000445519	SCV000537110	benign	Monogenic diabetes	2018-01-08	criteria provided, single submitter	research	ACMG criteria: PP3 (8 predictors), BS2 (107 controls in T2DM and 92 cases in type2diabetesgenetics.org), BS1 (1.53% in South Asian population in 1000g and 2.25% in ExAC South Asian pop), BP6 (Benign from Emory, but conflicting data (VUS from Chicago, LB from Illumina and Children's Mercy)=benign
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000515071	SCV000609894	likely benign	not provided	2017-08-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000515071	SCV001028041	benign	not provided	2024-12-16	criteria provided, single submitter	clinical testing
Mendelics	RCV000344820	SCV001140958	likely benign	Insulin-resistant diabetes mellitus AND acanthosis nigricans	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001132183	SCV001291837	benign	Leprechaunism syndrome	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	RCV001132184	SCV001291838	benign	Rabson-Mendenhall syndrome	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.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258250	SCV001435164	likely benign	Bailey-Bloch congenital myopathy		criteria provided, single submitter	research	The heterozygous p.Val1012Met variant in INSR has been identified in an individual with non-insulin-dependent diabetes mellitus and an unaffected individual (PMID: 2040394). This variant has also been identified in >2% of South Asian chromosomes and 11 homozygotes by ExAC (http://gnomad.broadinstitute.org/). Please note that individuals in ExAC may have type II diabetes. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for non-insulin-dependent diabetes mellitus NIDDM.
CeGaT Center for Human Genetics Tuebingen	RCV000515071	SCV004146433	benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	INSR: PP2, BS1, BS2
OMIM	RCV000015822	SCV000036089	uncertain significance	Type 2 diabetes mellitus	1999-03-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000175131	SCV002035090	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000515071	SCV002035602	likely benign	not provided		no assertion criteria provided	clinical testing