Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002905999 | SCV003652456 | likely pathogenic | Inborn genetic diseases | 2022-12-05 | criteria provided, single submitter | clinical testing | The c.4050dupG (p.Q1351Afs*21) alteration, located in exon 29 (coding exon 28) of the KIDINS220 gene, consists of a duplication of G at position 4050, causing a translational frameshift with a predicted alternate stop codon after 21 amino acids. This alteration occurs at the 3' terminus of the KIDINS220 gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 421aa of the protein._x000D_ _x000D_ Based on the available evidence, the KIDINS220 c.4050dupG (p.Q1351Afs*21) alteration is classified as likely pathogenic for autosomal dominant spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome; however, the association of this alteration with autosomal recessive KIDINS220-related ventriculomegaly and arthrogryposis is unlikely. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in one individual with KIDINS220-related neurodevelopmental disorder (internal Ambry data). Based on the available evidence, this alteration is classified as likely pathogenic. |