Submissions for variant NM_175914.5(HNF4A):c.393T>C (p.Asn131=)

gnomAD frequency: 0.00598  dbSNP: rs113308087

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030021	SCV000052676	likely benign	Maturity-onset diabetes of the young type 1	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely benign.
PreventionGenetics, part of Exact Sciences	RCV000248180	SCV000316594	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000401137	SCV000433894	likely benign	Familial hyperinsulinism	2018-01-12	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	RCV000030021	SCV000433895	benign	Maturity-onset diabetes of the young type 1	2018-01-12	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.
GeneDx	RCV000248180	SCV000730725	benign	not specified	2017-07-14	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000880936	SCV001024067	benign	not provided	2024-01-12	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002226657	SCV002505499	uncertain significance	Type 2 diabetes mellitus		criteria provided, single submitter	research	Mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. These are associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, no sufficient evidence was found for role of rs113308087 variant in T2DM.
Ambry Genetics	RCV002371790	SCV002624961	benign	Maturity onset diabetes mellitus in young	2017-11-16	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000880936	SCV004562208	benign	not provided	2023-10-14	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000248180	SCV002033841	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000880936	SCV002036949	likely benign	not provided		no assertion criteria provided	clinical testing