ClinVar Miner

Submissions for variant NM_000168.6(GLI3):c.4431dup (p.Glu1478Ter) (rs1057520063)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ali Lab, Centre for Genetic Disorders,Banaras Hindu University RCV000656366 SCV000743095 pathogenic Greig cephalopolysyndactyly syndrome 2015-01-13 criteria provided, single submitter research Single nucleotide insertion c.4431dupT (p.E1478X) in the sporadic case of postaxial polydactyly (PAP) introduce a premature stop codon leading to loss of C-terminal domain.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000432432 SCV000510665 pathogenic not provided 2016-07-15 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000656366 SCV000992566 pathogenic Greig cephalopolysyndactyly syndrome 2019-06-25 criteria provided, single submitter research
Invitae RCV000634034 SCV000755312 pathogenic Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome 2017-10-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GLI3 gene (p.Glu1478*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 103 amino acids of the GLI3 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Greig cephalopolysyndactyly syndrome (PMID: 24736735), as well as in an individual affected with only polydactyly (PMID: 26508445). In addition, a different variant (c.4432G>T) that also results in a premature translational stop signal at the same codon (p.Glu1478*) has been reported in an individual affected with Greig cephalopolysyndactyly syndrome (PMID: 20672375) A different truncation (p. Thr1488Lysfs*23) that lies downstream of this variant has been determined to be pathogenic (PMID: 24736735). This suggests that deletion of this region of the GLI3 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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