ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.1854C>G (p.Ile618Met)

dbSNP: rs193922591
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV001288068 SCV001474903 uncertain significance not provided 2020-07-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408483 SCV002722097 uncertain significance Maturity onset diabetes mellitus in young 2018-02-27 criteria provided, single submitter clinical testing The p.I618M variant (also known as c.1854C>G), located in coding exon 10 of the HNF1A gene, results from a C to G substitution at nucleotide position 1854. The isoleucine at codon 618 is replaced by methionine, an amino acid with highly similar properties. This variant was identified in an individual diagnosed with diabetes at age 38; his mother also had diabetes, but was not analyzed (Ng MC et al. Diabet. Med., 1999 Nov;16:956-63). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153306 SCV003843827 benign Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001288068 SCV004547709 uncertain significance not provided 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 618 of the HNF1A protein (p.Ile618Met). This variant is present in population databases (rs193922591, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of HNF1A-related conditions (PMID: 10588527, 32238361). ClinVar contains an entry for this variant (Variation ID: 36813). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on HNF1A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV005007898 SCV005634529 uncertain significance Diabetes mellitus type 1; Type 1 diabetes mellitus 20; Maturity-onset diabetes of the young type 3; Type 2 diabetes mellitus; Hepatic adenomas, familial; Nonpapillary renal cell carcinoma 2023-12-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030494 SCV000053165 not provided Maturity-onset diabetes of the young type 3 2015-10-02 no assertion provided clinical testing
ITMI RCV000121192 SCV000085362 not provided not specified 2013-09-19 no assertion provided reference population

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