ClinVar Miner

Submissions for variant NM_000095.3(COMP):c.1569C>G (p.Asn523Lys)

dbSNP: rs137852654
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000009767 SCV000996181 likely pathogenic Multiple epiphyseal dysplasia type 1 2018-08-01 criteria provided, single submitter clinical testing This variant has been previously reported as a disease causing heterozygous change in multiple affected individuals with multiple epiphyseal dysplasia (PMID: 9021009, 24595329). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.1569C>G (p.Asn523Lys) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.1569C>G (p.Asn523Lys) variant is classified as likely pathogenic.
Invitae RCV001851774 SCV002124210 pathogenic not provided 2022-04-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 523 of the COMP protein (p.Asn523Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with epiphyseal dysplasia (PMID: 9021009). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9189). 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009767 SCV000029988 pathogenic Multiple epiphyseal dysplasia type 1 1997-02-11 no assertion criteria provided literature only
GeneReviews RCV002054430 SCV002496191 not provided Multiple epiphyseal dysplasia no assertion provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.