ClinVar Miner

Submissions for variant NM_000168.6(GLI3):c.2119C>T (p.Pro707Ser) (rs121917716)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics, Erasmus University Medical Center RCV000508658 SCV000328910 likely pathogenic Hirschsprung disease 1 2016-11-18 no assertion criteria provided clinical testing
Genetic Services Laboratory, University of Chicago RCV000500441 SCV000594998 uncertain significance not specified 2016-12-28 criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000782254 SCV000920747 likely benign not provided 2018-09-16 no assertion criteria provided research
Invitae RCV000542657 SCV000630786 uncertain significance Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome 2018-11-19 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 707 of the GLI3 protein (p.Pro707Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs121917716, ExAC 0.03%). This variant has been reported in an individual affected with Greig syndrome (PMID: 9302279). ClinVar contains an entry for this variant (Variation ID: 13831). An experimental study has shown that this missense change partially disrupts the nuclear localization of GLI3 and reduces its transcriptional activity in a reporter assay (PMID: 19829694). In summary, this variant is a rare missense change that partially disrupts protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000014843 SCV000035098 pathogenic Greig cephalopolysyndactyly syndrome 1997-10-01 no assertion criteria provided literature only

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