Submissions for variant NM_002435.3(MPI):c.61A>G (p.Met21Val)

gnomAD frequency: 0.00006  dbSNP: rs376746368

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000821114	SCV000961858	uncertain significance	MPI-congenital disorder of glycosylation	2024-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 21 of the MPI protein (p.Met21Val). This variant is present in population databases (rs376746368, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with MPI-related conditions. ClinVar contains an entry for this variant (Variation ID: 663264). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx	RCV001796255	SCV002032537	uncertain significance	not provided	2021-06-04	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 27535533)
Fulgent Genetics, Fulgent Genetics	RCV000821114	SCV002776780	uncertain significance	MPI-congenital disorder of glycosylation	2021-07-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702457	SCV005204823	uncertain significance	not specified	2024-06-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003908109	SCV004724107	likely benign	MPI-related disorder	2022-10-24	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).