Submissions for variant NM_000207.3(INS):c.278A>G (p.Glu93Gly)

dbSNP: rs1057524907

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Translational Genomics Laboratory, University of Maryland School of Medicine	RCV000445381	SCV000537125	likely pathogenic	Monogenic diabetes	2016-03-18	criteria provided, single submitter	clinical testing	The c.278A>G variant in codon 93 (exon 3) of the insulin gene, INS, results in the substitution of Glutamic acid to Glycine. Missense variants in the INS gene are a common cause of permanent neonatal diabetes and a rare cause of a subtype of mature onset diabetes of the young (MODY) called MODY10 (17855560; 18192540; 18162506; 20226046; 25542748). The c.278A>G variant was not observed in the NHLBI Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium databases. Multiple lines of computational evidence (SIFT, Polyphen, MutationTaster, FATHMM, SVM, LR, CADD, GERP) predict this variant is probably damaging to the protein structure, function, or protein-protein interaction. In particular, the c.278A>G variant is in a highly-conserved residue located within the α-chain of the protein, and may be important for proper folding of the proinsulin molecule (18165206, 25542748). Additionally, there is little benign variation in this region among individuals in population databases and within the literature. ACMG Criteria = PM1, PM2, PP2, PP3
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003446061	SCV004174205	uncertain risk allele	Maturity-onset diabetes of the young type 10		criteria provided, single submitter	research	Potent mutations in the INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, as this mutation can cause beta cell destruction. However, no sufficient evidence is found to ascertain the role of this particular variant rs1057524907, yet.