Submissions for variant NM_002435.3(MPI):c.419T>C (p.Ile140Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003470168	SCV004193270	likely pathogenic	MPI-congenital disorder of glycosylation	2024-03-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526988	SCV005039889	uncertain significance	not specified	2024-03-15	criteria provided, single submitter	clinical testing	Variant summary: MPI c.419T>C (p.Ile140Thr) results in a non-conservative amino acid change located in the Phosphomannose isomerase type I, catalytic domain (IPR046457) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251462 control chromosomes. c.419T>C has been reported in the literature in at-least two siblings affected with Congenital Disorder Of Glycosylation Type 1B (example, Westphal_2001, Jones_2011). These data indicate that the variant may be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 11350186, 21811164). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 2676652). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.