Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Kasturba Medical College, |
RCV001250925 | SCV001167675 | likely pathogenic | Pseudoachondroplastic spondyloepiphyseal dysplasia syndrome | 2020-02-03 | criteria provided, single submitter | clinical testing | The variant is considered to be likely pathogenic as it qualifies following criteria of ACMG: PM1, PM2, PM5, PP2,PP3 and PP4 |
Invitae | RCV001383286 | SCV001582374 | pathogenic | not provided | 2020-06-26 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with arginine at codon 292 of the COMP protein (p.Cys292Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of pseudoachondroplasia (Invitae). In at least one individual the variant was observed to be de novo. 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. This variant disrupts the p.Cys292 amino acid residue in COMP. Other variant(s) that disrupt this residue have been observed in individuals with COMP-related conditions (PMID: 10405447, 30138938, 21965141), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Kasturba Medical College, |
RCV001805971 | SCV002053875 | pathogenic | Multiple epiphyseal dysplasia type 1 | criteria provided, single submitter | clinical testing |