Submissions for variant NM_139058.3(ARX):c.357_391del (p.Gly120fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002801305	SCV003198202	pathogenic	Developmental and epileptic encephalopathy, 1; Intellectual disability, X-linked, with or without seizures, arx-related	2022-05-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly120Asnfs*106) in the ARX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARX are known to be pathogenic (PMID: 19439424, 19738637). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ARX-related conditions. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV004064864	SCV004910839	pathogenic	Inborn genetic diseases	2024-02-20	criteria provided, single submitter	clinical testing	The c.357_391del35 (p.G120Nfs*106) alteration, located in exon 2 (coding exon 2) of the ARX gene, consists of a deletion of 35 nucleotides from position 357 to 391, causing a translational frameshift with a predicted alternate stop codon after 106 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.