Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778141 | SCV000914272 | uncertain significance | Leprechaunism syndrome | 2019-04-05 | criteria provided, single submitter | clinical testing | The INSR c.927_929delCAA (p.Asn309del) inframe deletion variant has been reported in one study in which it was found in a compound heterozygous state with a splice donor variant in one infant with congenital Donohue syndrome (Longo et al. 1995). Segregation analysis in this family revealed the infant inherited the p.Asn309del variant from his healthy father and the splice donor variant from his healthy mother. The p.Asn309del variant was absent from 10 controls and is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium but this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Characterization of fibroblasts from the affected infant revealed insulin binding of less than 10% of controls; the father also showed partial insulin binding impairment when skin fibroblasts were analyzed (Longo et al. 1995). Based on the limited evidence, the p.Asn309del variant is classified as a variant of unknown significance but suspicious for pathogenicity for Donohue syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |