ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.4136G>A (p.Arg1379His) (rs193922401)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000710386 SCV000840596 likely pathogenic not provided 2017-09-28 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV001249023 SCV001422930 likely pathogenic Monogenic diabetes 2020-01-22 no assertion criteria provided curation The p.Arg1379His (sometimes called p.Arg1380His) variant in ABCC8 has been reported in 12 individuals with Monogenic Diabetes and segregated with disease in 5 affected relatives from 2 families (PMID: 22210575, 23093687, 27271189, 21989597, 19342262, 17446535, 17389331; DOI: 10.1016/j.clinph.2015.04.103). Data from large population studies is insufficient to assess the frequency of this variant. Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. This variant has also been reported likely pathogenic in ClinVar (Variation ID: 585346). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Three additional variants, each with a different amino acid change at the same position, (p.Arg1379Leu, p.Arg1379Ser, and p.Arg1379Cys), have been reported in association with disease in the literature and ClinVar, supporting that a change at this position may not be tolerated (PMID: 18025464; Variation ID: 9105, 35614, 35615). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM5, PP1_Moderate, PP3, PS4_moderate (Richards 2015).

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