Submissions for variant NM_007118.4(TRIO):c.5822_5823insAG (p.Phe1942fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004784908	SCV005397157	likely pathogenic	Intellectual developmental disorder, autosomal dominant 63, with macrocephaly	2023-03-17	criteria provided, single submitter	clinical testing	This sequence variant is an insertion of two nucleotides (insAG) at coding positions 5822 and 5823 in exon 38 of 57 of the TRIO gene. This insertion introduces a premature termition sigl 27 codons downstream of a frameshift introduced at codon 1942. This variant is predicted to generate a non-functiol allele through either the expression of a truncated protein or a loss of TRIO expression due to nonsense mediated decay. This novel variant is absent from an online database of clinically annotated variants (ClinVar) and from the gnomAD population database (0 of approximately 250,000 alleles). This variant has not been observed in an individual affected by a TRIO-related disorder in the published literature, to our knowledge. Likewise, the functiol consequence of this variant has not been published, to our knowledge. However, haploinsufficiency in TRIO is a known mechanism of disease (ClinGen). Based upon the evidence, we consider this variant to be likely pathogenic. ACMG Criteria: PM2, PVS1