ClinVar Miner

Submissions for variant NM_001386140.1(MTTP):c.1868-2A>G

gnomAD frequency: 0.00001  dbSNP: rs760547155
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000801014 SCV000940763 likely pathogenic not provided 2023-10-14 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 14 of the MTTP 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 MTTP are known to be pathogenic (PMID: 8533758, 9671739). This variant is present in population databases (rs760547155, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MTTP-related conditions. ClinVar contains an entry for this variant (Variation ID: 646677). 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.
Natera, Inc. RCV001275667 SCV001460969 likely pathogenic Abetalipoproteinaemia 2020-09-16 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003392605 SCV004111280 likely pathogenic MTTP-related disorder 2024-02-29 no assertion criteria provided clinical testing The MTTP c.1868-2A>G variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was reported in an individual with abetalipoproteinemia (Dron et al. 2020. PubMed ID: 32041611 Table S4). This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD. Variants that disrupt the consensus acceptor splice site in MTTP are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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