ClinVar Miner

Submissions for variant NM_000900.5(MGP):c.56G>T (p.Cys19Phe)

dbSNP: rs1555094473
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001877559 SCV002142662 likely pathogenic not provided 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 19 of the MGP protein (p.Cys19Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant MGP-related spondyloepiphyseal dysplasia (PMID: 37923733). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1373923). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MGP function (PMID: 37923733). This variant disrupts the p.Cys19 amino acid residue in MGP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 37923733). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Care4Rare-SOLVE, CHEO RCV003389347 SCV004024152 uncertain significance Short stature; Platyspondyly; Short palm; Short distal phalanx of finger; Spondyloepiphyseal dysplasia 2023-08-09 criteria provided, single submitter research This heterozygous variant was identified in three family members with spondyloepiphyseal dysplasia. Functional work on this variant showed a deleterious effect and a knock in mouse model recapitulated the human phenotype. Publication link will be added upon publication.

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