ClinVar Miner

Submissions for variant NM_007289.4(MME):c.440-2A>C

gnomAD frequency: 0.00001  dbSNP: rs200435950
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497353 SCV000589411 likely pathogenic not provided 2020-12-16 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Observed as a heterozygous variant in a patient with late-onset CMT type 2 (Auer-Grumbach et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 27588448)
CeGaT Center for Human Genetics Tuebingen RCV000497353 SCV001335121 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000497353 SCV003525294 likely pathogenic not provided 2024-08-08 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the MME gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MME are known to be pathogenic (PMID: 26991897). This variant is present in population databases (rs200435950, gnomAD 0.004%). Disruption of this splice site has been observed in individual(s) with clinical features of MME-related conditions (PMID: 27588448). ClinVar contains an entry for this variant (Variation ID: 431858). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV000497353 SCV003832674 likely pathogenic not provided 2022-05-26 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV003492079 SCV004232634 likely pathogenic Charcot-Marie-Tooth disease axonal type 2T 2024-01-25 criteria provided, single submitter clinical testing

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