NM_000095.3(COMP):c.1317C>G (p.Asp439Glu) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 17, 2021
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:: RCV001377132.4

Allele description [Variation Report for NM_000095.3(COMP):c.1317C>G (p.Asp439Glu)]

NM_000095.3(COMP):c.1317C>G (p.Asp439Glu)

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.1317C>G (p.Asp439Glu)

Other names:

p.Asp439Glu

HGVS:

NC_000019.10:g.18786137G>C
NG_007070.1:g.10168C>G
NM_000095.2:c.1317C>G
NM_000095.3:c.1317C>GMANE SELECT
NP_000086.2:p.Asp439Glu
NC_000019.9:g.18896947G>C

Protein change:

D439E

Links:

dbSNP: rs368273443

NCBI 1000 Genomes Browser:

rs368273443

Molecular consequence:

NM_000095.3:c.1317C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001574372	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 17, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15756302, 26377240, 24595329, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001574372

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 17, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

COMP mutation screening as an aid for the clinical diagnosis and counselling of patients with a suspected diagnosis of pseudoachondroplasia or multiple epiphyseal dysplasia.

Kennedy J, Jackson G, Ramsden S, Taylor J, Newman W, Wright MJ, Donnai D, Elles R, Briggs MD.

Eur J Hum Genet. 2005 May;13(5):547-55. Review.

PubMed [citation]

PMID:: 15756302
PMCID:: PMC2673054

A pilot study of gene testing of genetic bone dysplasia using targeted next-generation sequencing.

Zhang H, Yang R, Wang Y, Ye J, Han L, Qiu W, Gu X.

J Hum Genet. 2015 Dec;60(12):769-76. doi: 10.1038/jhg.2015.112. Epub 2015 Sep 17.

PubMed [citation]

PMID:: 26377240

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001574372.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant disrupts the p.Asp439 amino acid residue in COMP. Other variant(s) that disrupt this residue have been observed in individuals with COMP-related conditions (PMID: 15756302, 24595329, 26377240), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. This missense change has been observed in individuals with clinical features of multiple epiphyseal dysplasia and/or pseudoachondroplasia (PMID: 24595329; Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 439 of the COMP protein (p.Asp439Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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