Submissions for variant NM_000458.4(HNF1B):c.1108G>A (p.Gly370Ser)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000429473	SCV000517254	uncertain significance	not provided	2021-06-28	criteria provided, single submitter	clinical testing	Observed in patients with MODY or renal cysts and diabetes syndrome; however, additional information is not available (Bellanne-Chantelot et al., 2005; Poitou et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22432796, 28453780, 21163139, 25700310, 27535533, 16249435, 24097065, 32041611)
Eurofins Ntd Llc (ga)	RCV000429473	SCV000707876	uncertain significance	not provided	2018-07-05	criteria provided, single submitter	clinical testing
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg	RCV000787092	SCV000926019	uncertain significance	Renal cysts and diabetes syndrome	2019-07-06	criteria provided, single submitter	literature only
Invitae	RCV000429473	SCV002386517	likely benign	not provided	2024-01-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282139	SCV002572098	likely benign	not specified	2022-08-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002450971	SCV002739429	uncertain significance	Maturity onset diabetes mellitus in young	2017-10-30	criteria provided, single submitter	clinical testing	The p.G370S variant (also known as c.1108G>A), located in coding exon 5 of the HNF1B gene, results from a G to A substitution at nucleotide position 1108. The glycine at codon 370 is replaced by serine, an amino acid with similar properties. This variant was detected in a cohort of individuals with maturity-onset diabetes of young(MODY)/renal cysts and diabetes (RCAD) (Bellanné-Chantelot C et al. Diabetes, 2005 Nov;54:3126-32; Poitou C et al. Transpl. Int., 2012 May;25:564-72). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear.
New York Genome Center	RCV002467781	SCV002764345	uncertain significance	Renal cysts and diabetes syndrome; Type 2 diabetes mellitus	2020-11-30	criteria provided, single submitter	clinical testing	The heterozygous c.1108G>A (p.Gly370Ser) missense variant identified in HNF1B has been previously reported in association with maturity-onset diabetes of the young type 5/ renal cysts and diabetes syndrome [PMID: 16249435;PMID: 2243279;PMID: 24097065]. Functional studies to evaluate the potential pathogenicity of this variant were not performed. This variant has been reported as a variant of uncertain in the ClinVar database [Variation ID:379811]. The variant has 0.001521 allele frequency in the African/African-American subpopulation of the gnomAD(v3) database (63 out of 41,432 heterozygous alleles, 1 homozygous allele). The affected Gly370 residue is not highly conserved and in silico tools provide conflicting interpretations about potential pathogenicity of this variant. Based on the available evidence, the c.1108G>A (p.Gly370Ser) missense variant in the HNF1B gene is reported as a variant of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003922733	SCV004742917	uncertain significance	HNF1B-related condition	2024-01-10	criteria provided, single submitter	clinical testing	The HNF1B c.1108G>A variant is predicted to result in the amino acid substitution p.Gly370Ser. This variant has been reported in individuals with maturity-onset diabetes of the young type 5, also referred to as renal cysts and diabetes syndrome (Bellanne-Chantelot et al. 2005. PubMed ID: 16249435; referred to as rs113042313, Elashi et al. 2022. PubMed ID: 36613572). It has also been reported an individual without diabetes (Supplementary Tables 2 and 3, Flannick et al. 2013. PubMed ID: 24097065). No family or functional studies were performed to help assess its pathogenicity. This variant is reported in 0.18% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.