Submissions for variant NM_000208.4(INSR):c.2736G>A (p.Arg912=)

gnomAD frequency: 0.00134  dbSNP: rs147125937

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193783	SCV000247619	uncertain significance	not specified	2014-11-11	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000733051	SCV000861068	uncertain significance	not provided	2018-05-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000733051	SCV001034400	benign	not provided	2023-10-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001132297	SCV001291952	likely benign	Insulin-resistant diabetes mellitus AND acanthosis nigricans	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 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	RCV001132298	SCV001291953	likely benign	Leprechaunism syndrome	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 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	RCV001132299	SCV001291954	likely benign	Rabson-Mendenhall syndrome	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000733051	SCV004146434	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	INSR: BP4, BP7
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003884389	SCV004698169	likely benign	Hyperinsulinism due to INSR deficiency		criteria provided, single submitter	research	Potent mutations in INSR gene can lead to insulin resistance, which presents as impaired glucose tolerance, early onset type 2 diabetes, post prandial hyperglycemia and increased insulin requirement in type 1 diabetes. These mutations in INSR gene can also predispose to coronary artery disease, metabolic syndrome, polycystic ovarian disease and non alcoholic fatty liver disease.However, the role of this particular variant rs147125937 with early onset diabetes mellitus is yet to be ascertained.
PreventionGenetics, part of Exact Sciences	RCV004541242	SCV004775623	likely benign	INSR-related disorder	2022-03-23	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).