ClinVar Miner

Submissions for variant NM_004771.4(MMP20):c.389C>T (p.Thr130Ile)

gnomAD frequency: 0.00180  dbSNP: rs61730849
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778295 SCV000914474 likely pathogenic Amelogenesis imperfecta hypomaturation type 2A2 2019-01-13 criteria provided, single submitter clinical testing The MMP20 c.389C>T (p.Thr130Ile) missense variant has been reported in three studies in which it is found in a total of four individuals with amelogenesis imperfecta, including in one in a homozygous state and in three in a compound heterozygous state (Gasse et al. 2013; Gasse et al. 2017; Kim et al. 2017). In all studies, one of the unaffected parents was shown to be heterozygous for the variant. Control data are unavailable for this variant which is reported at a frequency of 0.005575 in the European (Finnish) population from the Genome Aggregation Database. Of note, there are two homozygotes reported in the European (non-Finnish) population from this database. In HEK293 cells, the p.Thr130Ile variant showed reduced secretion into the enamel matrix with retention of proteolytic activity, suggesting reduced functional activity of the protein (Kim et al. 2017). Based on the evidence, the p.Thr130Ile variant is likely pathogenic for amelogenesis imperfecta. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV000896399 SCV001040488 likely benign not provided 2017-10-16 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000896399 SCV002009764 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000896399 SCV002497163 likely pathogenic not provided 2023-09-01 criteria provided, single submitter clinical testing MMP20: PM3:Strong, PM2:Supporting, PP3, PS3:Supporting
PreventionGenetics, part of Exact Sciences RCV003424333 SCV004116749 likely pathogenic MMP20-related disorder 2024-09-20 no assertion criteria provided clinical testing The MMP20 c.389C>T variant is predicted to result in the amino acid substitution p.Thr130Ile. This variant has been previously reported in the homozygous or compound heterozygous state in unrelated individuals with amelogenesis imperfecta (Gasse et al. 2013. PubMed ID: 23625376; Kim et al. 2017. PubMed ID: 28473773; Gasse et al. 2017. PubMed ID: 28659819; Wang et al. 2020. PubMed ID: 32495503). Functional studies of the c.389C>T (p.Thr130Ile) variant showed a reduced amount of the MMP20 protein but proteolytic activity was intact (Kim et al. 2017. PubMed ID: 28473773). This variant is reported in 0.56% of alleles in individuals of European (Finnish) descent in gnomAD, including two homozygous individuals. This variant is interpreted as likely pathogenic.

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