Submissions for variant NM_000252.3(MTM1):c.528+1G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003050663	SCV003443983	pathogenic	Severe X-linked myotubular myopathy	2022-04-06	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 7 of the MTM1 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 MTM1 are known to be pathogenic (PMID: 9305655, 10063835). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with X-linked myotubular myopathy (PMID: 9305655, 11793470). This variant is also known as G(582+1)A. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV004700921	SCV005201745	pathogenic	not provided	2024-01-02	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 34134972, 9305655, 11793470, 15725586)