Submissions for variant NM_000458.4(HNF1B):c.884G>A (p.Arg295His)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000713806	SCV000342177	uncertain significance	not provided	2016-07-14	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000713806	SCV000844443	likely pathogenic	not provided	2018-08-22	criteria provided, single submitter	clinical testing	Not found in the total gnomAD dataset, and the data is high quality (0/276870 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Damaging to protein function(s) relevant to disease mechanism.
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000787122	SCV000926051	pathogenic	Renal cysts and diabetes syndrome	2019-07-06	criteria provided, single submitter	literature only
Fulgent Genetics, Fulgent Genetics	RCV001535983	SCV001752653	pathogenic	Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma	2021-06-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000713806	SCV001785737	likely pathogenic	not provided	2022-05-09	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 16249435, 17924661, 34487217, 27838256, 15068978, 31131422, 31595705, Weckwerth2021[paper], 33574344, 34440516, 15509593)
Invitae	RCV000713806	SCV003283854	pathogenic	not provided	2022-05-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg295 amino acid residue in HNF1B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16249435, 23979948, 31825128). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 295 of the HNF1B protein (p.Arg295His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with HNF1B-related disorders and/or renal cysts and diabetes syndrome (PMID: 15068978, 16249435, 31131422, 33574344). ClinVar contains an entry for this variant (Variation ID: 288154). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HNF1B protein function. Experimental studies have shown that this missense change affects HNF1B function (PMID: 15509593).
Medical Genetics Center, Maternal and Child Health Hospital of Hubei Province	RCV000787122	SCV003915601	likely pathogenic	Renal cysts and diabetes syndrome	2022-01-04	criteria provided, single submitter	clinical testing