ClinVar Miner

Submissions for variant NM_000095.3(COMP):c.2152C>T (p.Arg718Trp)

dbSNP: rs28936368
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268837 SCV001448039 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001268837 SCV001588971 pathogenic not provided 2024-12-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 718 of the COMP protein (p.Arg718Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with multiple epiphyseal dysplasia (PMID: 12483304, 14684695, 21834907, 21965141, 24595329). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9198). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COMP protein function. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001268837 SCV001832279 pathogenic not provided 2019-11-21 criteria provided, single submitter clinical testing
GeneDx RCV001268837 SCV003924689 likely pathogenic not provided 2023-05-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24595329, 21965141, 17133256, 21834907, 18328978, 29162415, 15880723, 26691295, 21042783, 14684695, 32686688, 12483304)
Neuberg Centre For Genomic Medicine, NCGM RCV000009776 SCV004100353 likely pathogenic Multiple epiphyseal dysplasia type 1 criteria provided, single submitter clinical testing The missense variant p.R718W in COMP (NM_000095.3) has been reported previously in affected indviduals with multiple epihyseal dysplasia (Briggs MD et al,Jakkula E et al,Mabuchi A et al). It has been submitted to ClinVar as Pathogenic. It is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. In silico tools predict the variant to be damaging and the residue is semi conserved across species. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009776 SCV000029997 pathogenic Multiple epiphyseal dysplasia type 1 2003-12-01 no assertion criteria provided literature only
GeneReviews RCV002054432 SCV000086693 not provided Multiple epiphyseal dysplasia no assertion provided literature only
OMIM RCV001289465 SCV001477295 pathogenic Carpal tunnel syndrome 2 2003-12-01 no assertion criteria provided literature only

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