Submissions for variant NM_007118.4(TRIO):c.6092del (p.Phe2030_Leu2031insTer)

dbSNP: rs752676391

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001383860	SCV001583174	pathogenic	not provided	2017-11-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in TRIO are known to be pathogenic (PMID: 26721934). This variant has not been reported in the literature in individuals with TRIO-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Leu2031*) in the TRIO gene. It is expected to result in an absent or disrupted protein product.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV001775172	SCV002012491	uncertain significance	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome	2021-11-05	criteria provided, single submitter	research	ACMG codes: PVS1
Ambry Genetics	RCV004968154	SCV005520902	pathogenic	Inborn genetic diseases	2024-09-10	criteria provided, single submitter	clinical testing	The c.6092delT (p.L2031*) alteration, located in exon 41 (coding exon 41) of the TRIO gene, consists of a deletion of one nucleotide at position 6092, causing a translational frameshift with a predicted alternate stop codon at amino acid position 2031. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. for TRIO-related neurodevelopmental disorder with microcephaly; however, it is unlikely to be causative of TRIO-related neurodevelopmental disorder with macrocephaly. The TRIO c.6092delT alteration was flagged as a low confidence call in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.
GeneDx	RCV001383860	SCV005882098	pathogenic	not provided	2024-09-06	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26721934)