Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV002266699 | SCV002548770 | uncertain significance | Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome; Intellectual developmental disorder, autosomal dominant 63, with macrocephaly | 2021-09-08 | criteria provided, single submitter | clinical testing | The c.8686C>A (p.(Leu2896Met)) variant in TRIO has not previously been reported in the literature or public variant repositories (ClinVar and LOVD). It has been observed in two individuals across population databases (gnomAD v2.1 and v3.0, TOPMed freeze 5). The p.(Leu2896Met) variant occurs in the penultimate exon of this 57-exon gene and is located within the protein kinase domain [UniProt ID: O75962], which is not enriched for pathogenic variants in the literature and ClinVar. In silico algorithms predict conflicting effects of the variant on the encoded transcript. Based on the available evidence the c.8686C>A variant in TRIO is classified as a variant of unknown significance. |