ClinVar Miner

Submissions for variant NM_000207.3(INS):c.115C>T (p.Leu39Phe)

dbSNP: rs2133676660
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital RCV002466269 SCV002758648 likely pathogenic Maturity-onset diabetes of the young type 10 criteria provided, single submitter clinical testing A heterozygous likely pathogenic missense variant was identified in exon 2 of the INS gene (NM_000207.2:c.115C>T, p.Leu39Phe). Pathogenic variants in INS are a rare (<1%) cause of autosomal dominant Maturity-Onset Diabetes of the Young (MODY type 10) (https://www.ncbi.nlm.nih.gov/books/NBK500456). The INS p.Leu39Phe variant substitutes the leucine at position 39 with phenylalanine and has not been observed in large population studies (Genome Aggregation Database). This residue is within the insulin B chain (amino acids 25-54, UniProtKB # P01308), a critical functional domain. The majority of in silico tools predict this missense variant has a damaging effect. While the p.Leu39Phe variant has not been reported before, other missense changes at this position (p.Leu39Pro and p.Leu39Val) have been reported in individuals with neonatal diabetes (PMID: 24411943, PMID: 25781672). Different missense changes within this domain have been reported (p.Leu30Met, p.Leu30Arg, p.Val42Ala) in individuals with a MODY phenotype (PMID: 27659712, PMID: 20007936, PMID: 27634015).

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