ClinVar Miner

Submissions for variant NM_000458.4(HNF1B):c.202G>C (p.Gly68Arg)

dbSNP: rs767576616
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001248884 SCV001422564 uncertain significance Maturity onset diabetes mellitus in young 2020-01-22 criteria provided, single submitter curation The p.Gly68Arg variant in HNF1B has not been previously reported in individuals with MODY and has been identified in 0.04% (13/30610) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs767576616). This variant has been seen in the general population at a frequency high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gly68Arg variant is uncertain. ACMG/AMP Criteria applied: BA1, PP3 (Richards 2015).
Labcorp Genetics (formerly Invitae), Labcorp RCV002570390 SCV003449886 uncertain significance not provided 2022-02-06 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with HNF1B-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 972748). This variant is present in population databases (rs767576616, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 68 of the HNF1B protein (p.Gly68Arg).
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV001248884 SCV002754371 likely risk allele Maturity onset diabetes mellitus in young flagged submission research HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia. However no sufficient evidence is found to ascertain the role of this particular variant rs767576616, yet.

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