Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000192640 | SCV000246559 | pathogenic | X-linked lissencephaly with abnormal genitalia | 2014-11-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000798531 | SCV000938151 | pathogenic | Developmental and epileptic encephalopathy, 1; Intellectual disability, X-linked, with or without seizures, arx-related | 2018-11-21 | criteria provided, single submitter | clinical testing | This variant results in expansion of the p.Ala100-Ala115 alanine tract in ARX. Expansions of the alanine tract in ARX have been observed in individuals with ARX-related conditions (PMID: 11889467, 17664401, 23246292). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this polyalanine expansion results in protein mislocalization, aggregation, and loss of ARX protein function (PMID: 15533998). This variant has been observed in an individual with clinical features of ARX-related disease (PMID: 23583054). This variant is also known as c.333_335dup(GGC)8 in the literature. ClinVar contains an entry for this variant (Variation ID: 210327). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.312_335dup24, results in the insertion of eight amino acid(s) to the ARX protein (p.Ala108_Ala115dup), but otherwise preserves the integrity of the reading frame. |