Recommendation	How to test for monogenic diabetes
1	A targeted NGS approach is the preferred option for testing MODY and NDM to maximize diagnostic yield without significant cost and variant interpretation burden compared to gene agnostic genome sequencing. Genome sequencing can provide data for novel gene and non-coding variant discovery and allows re-analysis for newly associated genes and variants but is prohibitively expensive for many laboratories and requires significant bioinformatics expertise to manage the huge numbers of variants and give correct classifications.
2	Targeted panels should be designed to include all known causes of monogenic diabetes including mitochondrial diabetes, detect known non-coding mutations (located in promoters, deep introns and distal enhancers) and detect CNVs. A comprehensive gene panel that includes all recessively inherited genes is essential in countries and populations with high rates of consanguinity.
3	A separate MLPA assay for CNV detection or genotyping assay such as pyrosequencing for m.3243A>G detection is acceptable but comes at increased cost.
4	NDM testing services should offer a methylation-based assay such as MS-MLPA since 6q24 imprinting defects are a common cause of TNDM.
5	The high diagnostic yield for GCK in suspected GCK-MODY and KCNJ11, ABCC8 and INS in NDM, and the clinical utility of these diagnoses, justifies rapid Sanger sequencing of these genes initially in these scenarios.