NM_002427.4(MMP13):c.619T>G (p.Trp207Gly) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jan 3, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000303456.15

Allele description

NM_002427.4(MMP13):c.619T>G (p.Trp207Gly)

Gene:

MMP13:matrix metallopeptidase 13 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.2

Genomic location:

Preferred name:

NM_002427.4(MMP13):c.619T>G (p.Trp207Gly)

HGVS:

NC_000011.10:g.102954174A>C
NG_021404.1:g.6561T>G
NM_002427.4:c.619T>GMANE SELECT
NP_002418.1:p.Trp207Gly
NC_000011.9:g.102824903A>C
NM_002427.3:c.619T>G
P45452:p.Trp207Gly

Protein change:

W207G; TRP207GLY

Links:

UniProtKB: P45452#VAR_073418; OMIM: 600108.0005; dbSNP: rs140059558

NCBI 1000 Genomes Browser:

rs140059558

Molecular consequence:

NM_002427.4:c.619T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000341124	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Likely pathogenic (Aug 2, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24648384, 27576021 Citation Link,
SCV001586089	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 3, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24648384, 27576021, 28492532
SCV001872883	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 23, 2021)	germline	clinical testing	Citation Link,
SCV002023492	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 11, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	7	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type.

Bonafé L, Liang J, Gorna MW, Zhang Q, Ha-Vinh R, Campos-Xavier AB, Unger S, Beckmann JS, Le Béchec A, Stevenson B, Giedion A, Liu X, Superti-Furga G, Wang W, Spahr A, Superti-Furga A.

Am J Med Genet A. 2014 May;164A(5):1175-9. doi: 10.1002/ajmg.a.36431. Epub 2014 Mar 19.

PubMed [citation]

PMID:: 24648384

Metaphyseal dysplasia, Spahr type; missense MMP13 mutations in two Iraqi siblings.

Tadros S, Scott RH, Calder AD, Hurst JA.

Clin Dysmorphol. 2017 Jan;26(1):13-17.

PubMed [citation]

PMID:: 27576021

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000341124.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	PubMed (2)

#	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		7	not provided	not provided	not provided

From Invitae, SCV001586089.4

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

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 207 of the MMP13 protein (p.Trp207Gly). This variant is present in population databases (rs140059558, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive metaphyseal dysplasia, Spahr type (PMID: 24648384, 27576021; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 183687). 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 MMP13 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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

From GeneDx, SCV001872883.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24648384, 27576021, 31130284, 13915518)

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

From Revvity Omics, Revvity, SCV002023492.3

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

#	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: Aug 4, 2024

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