Submissions for variant NM_000208.4(INSR):c.2665C>T (p.Arg889Trp)

gnomAD frequency: 0.00021  dbSNP: rs76077021

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000361037	SCV000333614	uncertain significance	not provided	2015-08-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765478	SCV000896769	uncertain significance	Insulin-resistant diabetes mellitus AND acanthosis nigricans; Hyperinsulinism due to INSR deficiency; Leprechaunism syndrome; Rabson-Mendenhall syndrome	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000361037	SCV002039055	uncertain significance	not provided	2021-06-14	criteria provided, single submitter	clinical testing	Identified in a non-obese pregnant woman with a diabetes and reported as a variant of uncertain significance in published literature (Zubkova et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30663027, 27535533)
Invitae	RCV000361037	SCV003278556	likely benign	not provided	2023-07-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003391030	SCV004120332	uncertain significance	INSR-related condition	2023-06-27	criteria provided, single submitter	clinical testing	The INSR c.2665C>T variant is predicted to result in the amino acid substitution p.Arg889Trp. This variant was reported as a variant of uncertain significance in an individual with gestational diabetes (Zubkova et al. 2019. PubMed ID: 30663027). This variant is reported in 0.034% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-7141705-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.