ClinVar Miner

Submissions for variant NM_001382.4(DPAGT1):c.1A>C (p.Met1Leu) (rs1057521151)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438342 SCV000521254 likely pathogenic not provided 2017-01-10 criteria provided, single submitter clinical testing The c.1A>C variant in the DPAGT1 gene has been reported previously in an affected individual diagnosed with myasthenia syndrome and intellectual disability, and her similar but less severely affected brother who were compound heterozygous for the c.1A>C variant and another variant (Selcen et al., 2014). As this variant changes the translation initiator Methionine codon, the resultant protein is described as p.Met1?, using a question mark to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if an abnormal protein is produced using an alternate Methionine. Selcen et al., (2014) demostrated a 60% reduction in protein expression for the c.1A>G variant and suggests an alternative start site. The c.1A>C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.1A>G variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000686050 SCV000813553 uncertain significance Congenital disorder of glycosylation type 1J; Congenital myasthenic syndrome 13 2018-07-11 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the DPAGT1 mRNA. The next in-frame methionine is located at codon 9. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another DPAGT1 variant in two siblings affected with congenital myasthenic syndrome (PMID: 24759841). ClinVar contains an entry for this variant (Variation ID: 381709). 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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