ClinVar Miner

Submissions for variant NM_004771.4(MMP20):c.910G>A (p.Ala304Thr)

gnomAD frequency: 0.00153  dbSNP: rs148818720
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000395040 SCV000366488 uncertain significance Amelogenesis imperfecta hypomaturation type 2A2 2017-04-27 criteria provided, single submitter clinical testing The MMP20 c.910G>A (p.Ala304Thr) missense variant has been reported in a single case study in which it was found in a homozygous state in two siblings whose parents were both heterozygous carriers of the variant (Lee et al. 2010). In vitro functional experiments showed that this variant produces a protein that is catalytically active, but has decreased expression compared to wild type MMP20. The p.Ala304Thr variant was absent from 100 controls and is reported at a frequency of 0.00298 in the European population of the 1000 Genomes Project. The evidence for this variant is limited. The p.Ala304Thr variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity 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 RCV001850596 SCV002278113 uncertain significance not provided 2021-09-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 304 of the MMP20 protein (p.Ala304Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs148818720, ExAC 0.2%). This variant has been observed in individual(s) with melogenesis imperfecta (PMID: 19966041). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 301942). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this variant affects MMP20 function (PMID: 19966041). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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