Submissions for variant NM_000458.4(HNF1B):c.1006C>G (p.His336Asp)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000731270	SCV000859066	uncertain significance	not provided	2018-01-02	criteria provided, single submitter	clinical testing
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV001125735	SCV000926034	uncertain significance	Renal cysts and diabetes syndrome	2019-07-06	criteria provided, single submitter	literature only
CeGaT Center for Human Genetics Tuebingen	RCV000731270	SCV001151275	uncertain significance	not provided	2022-12-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001125735	SCV001284837	benign	Renal cysts and diabetes syndrome	2017-04-28	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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
Invitae	RCV000731270	SCV002384096	likely benign	not provided	2024-01-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002422628	SCV002721829	uncertain significance	Maturity onset diabetes mellitus in young	2017-01-09	criteria provided, single submitter	clinical testing	The p.H336D variant (also known as c.1006C>G), located in coding exon 4 of the HNF1B gene, results from a C to G substitution at nucleotide position 1006. The histidine at codon 336 is replaced by aspartic acid, an amino acid with similar properties. This alteration was first described in two unrelated patients with renal hypodysplasia (RHD) associated with chronic renal insufficiency; the father and brother of one were each heterozygous for the alteration but had normal renal evaluations, including ultrasound and biochemical measurements (Weber S et al. J. Am. Soc. Nephrol., 2006 Oct;17:2864-70). In a MODY family, which included a proband with renal and urogenital anomalies, this alteration was identified in three of four individual's with a history of diabetes; however, an HNF1A alteration at a canonical splice site was present in all four diabetic family members (Karges B et al. Diabetes Care, 2007 Jun;30:1613-4). This alteration has been reported in an additional four individuals with congenital anomalies of the kidney and urinary tract (CAKUT); however, given the presence of this alteration in population databases, the authors were not convinced that p.H336D was causative (Hwang DY et al. Kidney Int., 2014 Jun;85:1429-33; Nicolaou N et al. Kidney Int., 2016 Feb;89:476-86). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000731270	SCV004235300	uncertain significance	not provided	2023-03-31	criteria provided, single submitter	clinical testing
Gharavi Laboratory, Columbia University	RCV000731270	SCV000920748	likely benign	not provided	2018-09-16	no assertion criteria provided	research