ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.2456G>A (p.Arg819His) (rs773985005)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000344148 SCV000470607 uncertain significance Ehlers-Danlos syndrome, procollagen proteinase deficient 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000394670 SCV000470608 uncertain significance Osteogenesis Imperfecta, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000798674 SCV000938300 uncertain significance Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 819 of the COL1A2 protein (p.Arg819His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs773985005, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in combination with another COL1A2 variant in an individual affected with osteogenesis imperfecta (PMID: 25944380). ClinVar contains an entry for this variant (Variation ID: 360962). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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