Submissions for variant NM_005321.3(H1-4):c.414dup (p.Lys139fs)

dbSNP: rs1581429403

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Tartaglia Lab, Genetics and Rare Diseases Research Division, Bambino Gesu' Children's Hospital	RCV000984019	SCV000925232	pathogenic	Rahman syndrome	2019-05-01	criteria provided, single submitter	research
Ambry Genetics	RCV001266839	SCV001445019	likely pathogenic	Inborn genetic diseases	2018-06-06	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268306	SCV001447136	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000984019	SCV004801444	pathogenic	Rahman syndrome	2020-05-01	criteria provided, single submitter	clinical testing	The HIST1H1E c.414dupC p.(Lys139GlnfsTer57) variant causes a shift in the protein reading frame that is predicted to result in premature termination of the protein. This frameshift event occurs in a mutational hotspot in the carboxy terminal domain of the gene (Burkardt et al. 2019) and it is predicted to result in an expressed, truncated protein that contains the recurrent 38 amino acid carboxy-terminal motif shared among affected individuals (Flex et al. 2019). This variant has been identified in individuals with a phenotype consistent with Rahman syndrome, in at least one of whom, the variant occurred in a de novo state (Flex et al. 2019). This variant is not observed in version 2.1.1 of the Genome Aggregation Database. The variant was identified in a de novo state in the proband. Based on the available evidence the c.414dupC p.(Lys139GlnfsTer57) variant is classified as pathogenic for Rahman syndrome.
GeneReviews	RCV000984019	SCV001468683	not provided	Rahman syndrome		no assertion provided	literature only