Submissions for variant NM_175914.5(HNF4A):c.1176C>T (p.Asn392=)

gnomAD frequency: 0.00033  dbSNP: rs141448616

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000270831	SCV000433900	uncertain significance	Familial hyperinsulinism	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	RCV000309520	SCV000433901	likely benign	Maturity-onset diabetes of the young 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000884368	SCV001027743	likely benign	not provided	2023-10-24	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000884368	SCV001144202	benign	not provided	2019-03-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000884368	SCV002525352	likely benign	not provided	2021-09-27	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Ambry Genetics	RCV002328864	SCV002635992	likely benign	Maturity onset diabetes mellitus in young	2022-04-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002328864	SCV003806246	benign	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	Potent mutations in HNF4A are associated with poor insulin secretion in response to hyperglycemia. Associated with MODY1. Patients initially respond well to sulfonylureas but eventually become insulin dependent. However, more evidence is required to ascertain the role of this particular variant rs141448616 in MODY, yet.
PreventionGenetics, part of Exact Sciences	RCV003932352	SCV004752481	likely benign	HNF4A-related disorder	2019-06-26	criteria provided, single submitter	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).