ClinVar Miner

Submissions for variant NM_000207.3(INS):c.137G>A (p.Arg46Gln)

dbSNP: rs121908260
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851851 SCV002297001 likely pathogenic not provided 2023-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 46 of the INS protein (p.Arg46Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant maturity-onset diabetes of the young type (PMID: 18192540, 20226046, 28478482). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13391). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects INS function (PMID: 20948967, 25423173). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV003445068 SCV004174195 uncertain significance Diabetes mellitus, permanent neonatal 4 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, mutations in this gene can cause beta cell destruction.Sufficient evidence is found to confer the association of this particular variant R46Q/ rs121908260 with permanent neonatal diabetes mellitus.
OMIM RCV000014323 SCV000034572 pathogenic Maturity-onset diabetes of the young type 10 2008-04-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000014323 SCV000091150 not provided Maturity-onset diabetes of the young type 10 no assertion provided not provided

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