ClinVar Miner

Submissions for variant NM_000095.3(COMP):c.1754C>T (p.Thr585Met)

dbSNP: rs312262900
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001388112 SCV001588972 pathogenic not provided 2022-02-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on COMP function (PMID: 17570134, 23956175). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COMP protein function. ClinVar contains an entry for this variant (Variation ID: 40995). This missense change has been observed in individuals with COMP-related skeletal dysplasia (PMID: 9463320, 11565064). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 585 of the COMP protein (p.Thr585Met).
Blueprint Genetics RCV001388112 SCV001832239 pathogenic not provided 2018-01-08 criteria provided, single submitter clinical testing
GeneReviews RCV000033887 SCV000057795 not provided Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome no assertion provided literature only
GeneReviews RCV002054553 SCV000086690 not provided Multiple epiphyseal dysplasia no assertion provided literature only

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