Submissions for variant NM_002435.3(MPI):c.1053+2T>C

dbSNP: rs2141208760

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002007264	SCV002232271	pathogenic	MPI-congenital disorder of glycosylation	2021-03-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MPI protein. Other variant(s) that disrupt this region (p.Ala363Hisfs*9) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MPI-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 7 of the MPI gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.