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NM_000095.3(COMP):c.1403G>C (p.Cys468Ser) AND Multiple epiphyseal dysplasia type 1

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 26, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001270873.4

Allele description [Variation Report for NM_000095.3(COMP):c.1403G>C (p.Cys468Ser)]

NM_000095.3(COMP):c.1403G>C (p.Cys468Ser)

Gene:
COMP:cartilage oligomeric matrix protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.11
Genomic location:
Preferred name:
NM_000095.3(COMP):c.1403G>C (p.Cys468Ser)
HGVS:
  • NC_000019.10:g.18786051C>G
  • NG_007070.1:g.10254G>C
  • NM_000095.3:c.1403G>CMANE SELECT
  • NP_000086.2:p.Cys468Ser
  • NC_000019.9:g.18896861C>G
  • NM_000095.2:c.1403G>C
Protein change:
C468S
Links:
dbSNP: rs137852651
NCBI 1000 Genomes Browser:
rs137852651
Molecular consequence:
  • NM_000095.3:c.1403G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Multiple epiphyseal dysplasia type 1
Identifiers:
MONDO: MONDO:0007561; MedGen: C1838280; Orphanet: 93308; OMIM: 132400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001451650Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)		Likely pathogenic
(Apr 26, 2019) 		unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations.

Briggs MD, Chapman KL.

Hum Mutat. 2002 May;19(5):465-78. Review.

PubMed [citation]
PMID:
11968079

The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding.

Tan K, Duquette M, Joachimiak A, Lawler J.

FASEB J. 2009 Aug;23(8):2490-501. doi: 10.1096/fj.08-128090. Epub 2009 Mar 10.

PubMed [citation]
PMID:
19276170
PMCID:
PMC2717772
See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001451650.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The COMP c.1403G>C (p.Cys468Ser) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not reported in the Genome Aggregation Database in a region of good sequencing coverage, so the variant is presumed to be rare. Functional studies of the p.Cys468Ser variant have not been conducted, but it affects the seventh type 3 calcium-binding repeat. These repeats play an important role in protein function and are a common site of pathogenic variants, particularly missense variants (Briggs et al. 2002; Tan et al. 2009; Jackson et al. 2012). Cys468 also participates in a disulfide bond. Multiple in silico tools consistently predict a deleterious effect of the p.Cys468Ser variant, and another amino acid change at the same position has been reported as causative for pseudoachondroplasia (Hecht et al. 1995; Xie et al. 2013). Based on the collective evidence, the p.Cys468Ser variant is classified as likely pathogenic for multiple epiphyseal dysplasia.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 9, 2023