Submissions for variant NM_175914.5(HNF4A):c.439G>A (p.Val147Ile)

gnomAD frequency: 0.00025  dbSNP: rs142204928

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000490471	SCV000267357	uncertain significance	Type 2 diabetes mellitus	2016-03-18	criteria provided, single submitter	reference population
Illumina Laboratory Services, Illumina	RCV000340715	SCV000433896	likely benign	Familial hyperinsulinism	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000030023	SCV000433897	likely benign	Maturity-onset diabetes of the young type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Athena Diagnostics	RCV000516787	SCV000613656	benign	not specified	2016-11-14	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000490471	SCV001435151	likely benign	Type 2 diabetes mellitus		criteria provided, single submitter	research	The heterozygous p.Val147Ile variant in HNF4A has been identified in 3 Philippino siblings from 1 family with maturity onset diabetes of the young and 2 individuals without diabetes mellitus (PMID: 15281001, 24097065), but has also been identified in >1% of South Asian chromosomes and 4 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 autosomal dominant diabetes mellitus type 2.
GeneDx	RCV000117239	SCV001753226	benign	not provided	2020-02-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32621647, 31216263, 25041077, 27080136, 27535533, 27810688, 15281001, 24097065)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000117239	SCV002461206	benign	not provided	2024-12-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326694	SCV002628803	benign	Maturity onset diabetes mellitus in young	2021-04-27	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.
CeGaT Center for Human Genetics Tuebingen	RCV000117239	SCV004183910	benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	HNF4A: BP4, BS1, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030023	SCV000052678	not provided	Maturity-onset diabetes of the young type 1	2015-10-02	no assertion provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000516787	SCV002033998	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000117239	SCV002036591	likely benign	not provided		no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000516787	SCV002067856	benign	not specified	2019-05-02	no assertion criteria provided	clinical testing