Submissions for variant NM_000545.8(HNF1A):c.998_1013del (p.Val333fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003229266	SCV003926046	likely pathogenic	not provided	2022-11-22	criteria provided, single submitter	clinical testing	Frameshift 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); Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003317670	SCV004020723	pathogenic	Maturity onset diabetes mellitus in young	2023-06-27	criteria provided, single submitter	clinical testing	Variant summary: HNF1A c.998_1013del16 (p.Val333AlafsX4) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 251438 control chromosomes (gnomAD). To our knowledge, no occurrence of c.998_1013del16 in individuals affected with Maturity Onset Diabetes Of The Young 3 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.