Submissions for variant NM_000458.4(HNF1B):c.244G>A (p.Asp82Asn)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724384	SCV000224226	uncertain significance	not provided	2018-03-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000314789	SCV000402434	benign	Renal cysts and diabetes syndrome	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000173137	SCV000539309	uncertain significance	not specified	2016-10-27	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant is classified in HGMD as DM, related to HNF1B-related disease (reported in one patient, phenotype not specified). This variant is classified in ClinVar with 1 star as VUS by Emory. It is present in ExAC with a Max MAF of 0.12%.
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000314789	SCV000926171	uncertain significance	Renal cysts and diabetes syndrome	2019-07-06	criteria provided, single submitter	literature only
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001174365	SCV001337503	uncertain significance	Monogenic diabetes	2019-01-11	criteria provided, single submitter	research	ACMG criteria: PP3 (REVEL 0.890 + 7 predictors); PP4 (19639018, 26899772; variant also identified in patient in PMID: 24897035 (no clinical info, can't tell if overlap with other papers); BS2 (12 cases and 15 controls in T2Dgenes); BS1 (MAF in gnomAD EurNF population is 0.09%; 0.14% in ESP European pop)= scores as benign, but going to call as VUS given case reports and predictors (conflicting evidence).
Athena Diagnostics	RCV000173137	SCV001475669	benign	not specified	2019-12-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000724384	SCV001824843	uncertain significance	not provided	2023-01-05	criteria provided, single submitter	clinical testing	Reported in unrelated patients in published literature, including one individual with hyperuricemia, bilateral renal cysts and dysplasia, and stage 1 chronic kidney disease (Okorn et al., 2019) and an individual whose clinical information was not provided (Yu 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: 19639018, 26899772, 24897035, 27634015, 31264968, 30666461, 34426522, 32041611)
Invitae	RCV000724384	SCV002431991	likely benign	not provided	2024-01-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444693	SCV002732084	likely benign	Maturity onset diabetes mellitus in young	2018-12-20	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.
Revvity Omics, Revvity	RCV000724384	SCV003808684	uncertain significance	not provided	2022-10-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000724384	SCV004144497	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing	HNF1B: BS1:Supporting, BS2
PreventionGenetics, part of Exact Sciences	RCV003937545	SCV004747536	uncertain significance	HNF1B-related disorder	2024-02-16	criteria provided, single submitter	clinical testing	The HNF1B c.244G>A variant is predicted to result in the amino acid substitution p.Asp82Asn. This variant has been reported in patients with HNF1B-related disease but its pathogenicity was not conclusive (Faguer et al. 2014. PubMed ID: 24897035; Brahm et al. 2016. PubMed ID: 27634015; Yu et al. 2019. PubMed ID: 31264968, supplementary table 6; Okorn et al. 2019. PubMed ID: 30666461; Kanda et al. 2016. PubMed ID: 26899772; Zuber et al. 2009. PubMed ID: 19639018). This variant is reported in 0.11% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000724384	SCV001798926	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center	RCV001844814	SCV001877065	uncertain significance	Autosomal dominant polycystic liver disease	2021-09-01	no assertion criteria provided	research
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000724384	SCV001926999	likely benign	not provided		no assertion criteria provided	clinical testing