Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Rady Children's Institute for Genomic Medicine, |
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 | |
Gene |
RCV002054430 | SCV002496191 | not provided | Multiple epiphyseal dysplasia | no assertion provided | literature only |