ClinVar Miner

Submissions for variant NM_002381.5(MATN3):c.359C>T (p.Thr120Met)

dbSNP: rs397515546
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001093350 SCV001250287 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital RCV001093350 SCV001449729 likely pathogenic not provided 2019-01-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001093350 SCV001591723 pathogenic not provided 2024-02-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 120 of the MATN3 protein (p.Thr120Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with multiple epiphyseal dysplasia (PMID: 14729835, 15459972, 21965141). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 65664). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MATN3 protein function. For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV000055878 SCV002073078 pathogenic Multiple epiphyseal dysplasia type 5 criteria provided, single submitter clinical testing The missense variant p.T120M in MATN3 (NM_002381.5) has been reported in multiple affected individuals and shows incomplete penetrance (Mabuchi A et al; Jackson GC et al; Kim OH et al). It has been submitted to ClinVar as Pathogenic.The p.T120M variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.T120M missense variant is predicted to be damaging by both SIFT and PolyPhen2. The threonine residue at codon 120 of MATN3 is conserved in all mammalian species. The nucleotide c.359 in MATN3 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic
Neuberg Centre For Genomic Medicine, NCGM RCV001375669 SCV004100565 pathogenic Spondyloepimetaphyseal dysplasia, matrilin-3 type criteria provided, single submitter clinical testing The missense variant p.T120M in MATN3 (NM_002381.5) has been reported in multiple affected individuals and shows incomplete penetrance (Mabuchi A et al,Jackson GC et al,Kim OH et al). It has been submitted to ClinVar as Pathogenic. The p.T120M variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.T120M missense variant is predicted to be damaging by both SIFT and PolyPhen2. The threonine residue at codon 120 of MATN3 is conserved in all mammalian species. The nucleotide c.359 in MATN3 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV002054898 SCV000086881 not provided Multiple epiphyseal dysplasia no assertion provided literature only European-based studies have identified p.Arg121Trp in 12/33 and p.Thr120Met in 5/33 affected individuals (total = 52%) [Chapman et al 2001; Mostert et al 2003; Jackson et al 2004; Cotterill et al 2005; Fresquet et al 2007; Jackson et al 2012; Author, unpublished data]. In a Japanese population, p.Arg121Trp was identified in 3/9 and p.Thr120Met in 3/9 affected individuals (total = 66%) [Mabuchi et al 2004, Itoh et al 2006]. In a Korean study, p.Arg121Trp was identified in 20/30 and p.Thr120Met was identified in 4/30 affected individuals (total = 80%) [Kim et al 2011].
OMIM RCV000055878 SCV001572595 pathogenic Multiple epiphyseal dysplasia type 5 2004-01-01 no assertion criteria provided literature only
OMIM RCV001375669 SCV001572596 pathogenic Spondyloepimetaphyseal dysplasia, matrilin-3 type 2004-01-01 no assertion criteria provided literature only

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