NM_000493.4(COL10A1):c.1853G>T (p.Gly618Val) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 25, 2022
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:: RCV001378529.7

Allele description [Variation Report for NM_000493.4(COL10A1):c.1853G>T (p.Gly618Val)]

NM_000493.4(COL10A1):c.1853G>T (p.Gly618Val)

Genes:

NT5DC1:5'-nucleotidase domain containing 1 [Gene - HGNC]
COL10A1:collagen type X alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.1

Genomic location:

Preferred name:

NM_000493.4(COL10A1):c.1853G>T (p.Gly618Val)

HGVS:

NC_000006.12:g.116120263C>A
NG_008032.1:g.10871G>T
NG_021351.1:g.24428C>A
NG_021351.2:g.24412C>A
NM_000493.4:c.1853G>TMANE SELECT
NM_001424106.1:c.1853G>T
NM_001424107.1:c.1853G>T
NM_152729.3:c.529+2318C>AMANE SELECT
NP_000484.2:p.Gly618Val
NP_001411035.1:p.Gly618Val
NP_001411036.1:p.Gly618Val
NC_000006.11:g.116441426C>A

Protein change:

G618V

Links:

dbSNP: rs2114277897

NCBI 1000 Genomes Browser:

rs2114277897

Molecular consequence:

NM_152729.3:c.529+2318C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000493.4:c.1853G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001424106.1:c.1853G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001424107.1:c.1853G>T - 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
SCV001576114	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15695517, 7876225, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001576114

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 25, 2022)

germline

clinical testing

PubMed (3)
[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

Misfolding of collagen X chains harboring Schmid metaphyseal chondrodysplasia mutations results in aberrant disulfide bond formation, intracellular retention, and activation of the unfolded protein response.

Wilson R, Freddi S, Chan D, Cheah KS, Bateman JF.

J Biol Chem. 2005 Apr 22;280(16):15544-52. Epub 2005 Feb 4.

PubMed [citation]

PMID:: 15695517

Type X collagen multimer assembly in vitro is prevented by a Gly618 to Val mutation in the alpha 1(X) NC1 domain resulting in Schmid metaphyseal chondrodysplasia.

Chan D, Cole WG, Rogers JG, Bateman JF.

J Biol Chem. 1995 Mar 3;270(9):4558-62.

PubMed [citation]

PMID:: 7876225

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001576114.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects COL10A1 function (PMID: 7876225, 15695517). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1067305). This missense change has been observed in individuals with clinical features of Schmid metaphyseal chondrodysplasia (PMID: 7876225; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 618 of the COL10A1 protein (p.Gly618Val).

#	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: Sep 29, 2024

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