ClinVar Miner

Submissions for variant NM_000458.4(HNF1B):c.541C>T (p.Arg181Ter)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413356 SCV000490558 pathogenic not provided 2023-07-24 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15068978, 24897035, 32164334, 30860651, 32708349, 21380624, 16249435, 15930087, 29100090, 27615128, 16133182, 28324003, 34136434)
Eurofins Ntd Llc (ga) RCV000413356 SCV000707672 pathogenic not provided 2017-04-10 criteria provided, single submitter clinical testing
Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg RCV000787179 SCV000926109 pathogenic Renal cysts and diabetes syndrome 2019-07-06 criteria provided, single submitter literature only
Invitae RCV000413356 SCV002200810 pathogenic not provided 2022-06-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372381). This premature translational stop signal has been observed in individual(s) with HNF1B-related conditions (PMID: 15068978, 21380624, 29100090, 32164334). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg181*) in the HNF1B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HNF1B are known to be pathogenic (PMID: 9398836, 12148114, 15068978, 20378641).
Ambry Genetics RCV002348127 SCV002647920 pathogenic Maturity onset diabetes mellitus in young 2018-04-25 criteria provided, single submitter clinical testing The p.R181* pathogenic mutation (also known as c.541C>T), located in coding exon 2 of the HNF1B gene, results from a C to T substitution at nucleotide position 541. This changes the amino acid from an arginine to a stop codon within coding exon 2. This mutation was identified in an individual with diabetes diagnosed at age 33 years and kidney abnormalities; the individual's child was diagnosed with a unilateral dysplastic multicystic kidney prenatally (Bellanné-Chantelot C et al. Ann. Intern. Med., 2004 Apr;140:510-7). In another family, this mutation was identified in a father with diabetes and renal cysts and three of his young children also with renal cysts (Edghill EL et al. J. Med. Genet., 2006 Jan;43:84-90). Finally, this mutation was identified in a child with renal hypodysplasia (Thomas R et al. Pediatr. Nephrol., 2011 Jun;26:897-903). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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