ClinVar Miner

Submissions for variant NM_000458.4(HNF1B):c.1025C>T (p.Ser342Phe)

gnomAD frequency: 0.00001  dbSNP: rs780035561
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000386201 SCV000340049 uncertain significance not provided 2016-02-29 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001125734 SCV001284836 likely benign Renal cysts and diabetes syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genetic Services Laboratory, University of Chicago RCV001820823 SCV002071953 uncertain significance not specified 2021-10-25 criteria provided, single submitter clinical testing DNA sequence analysis of the HNF1B gene demonstrated a sequence change, c.1025C>T, in exon 4 that results in an amino acid change, p.Ser342Phe. This sequence change has been described in the gnomAD database with a frequency of 0.007% in the South Asian subpopulation (dbSNP rs780035561). The p.Ser342Phe change affects a moderately conserved amino acid residue located in a domain of the HNF1B protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ser342Phe substitution. This sequence change does not appear to have been previously described in individuals with HNF1B-related disorders, however, a different amino acid change affecting the same position, p.Ser342Phe, has been identified in the heterozygous state in an individual with congenital anomalies of the kidney and urinary tract (PMID: 24429398, 30143558). This p.Ser342Phe variant was inherited from the individual’s mother with unknown phenotype. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Ser342Phe change remains unknown at this time.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002465609 SCV002754372 uncertain risk allele Maturity onset diabetes mellitus in young criteria provided, single submitter 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 rs780035561, yet.

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