ClinVar Miner

Submissions for variant NM_000026.4(ADSL):c.1187G>A (p.Arg396His) (rs763542069)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186690 SCV000240256 pathogenic not provided 2013-08-06 criteria provided, single submitter clinical testing p.Arg396His (CGC>CAC): c.1187 G>A in exon 11 of the ADSL gene (NM_000026.2) The Arg396His mutation has been reported previously in patients with ADSL deficiency who harbored a second disease-causing mutation in the ADSL gene (Castro et al., 2002; Zikonova et al., 2010). It alters a highly conserved position at the entrance to the active site of the ADSL enzyme, and functional studies indicate that this mutation reduces ADSL enzyme activity (Ariyananda et al., 2009; Zikonova et al., 2010). The variant is found in INFANT-EPI panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000779373 SCV000915974 likely pathogenic Adenylosuccinate lyase deficiency 2017-05-05 criteria provided, single submitter clinical testing The ADSL c.1187G>A (p.Arg396His) missense variant has been reported in two studies in a compound heterozygous state with other missense variants in two individuals with adenylosuccinase deficiency (Castro et al. 2002; Zikanova et al. 2010). One individual presented with intellectual disability while the other presented a neonatal fatal form of the disorder. Control data are unavailable for the p.Arg396His variant, which is reported at a frequency of 0.00012 in the Latino population of the Genome Aggregation Database. Functional studies using biochemical and biophysical techniques have shown the p.Arg396His variant to have low residual enzyme activity and increased thermal instability (Ariyananda et al. 2009; Zikanova et al. 2010; Ariyananda et al. 2011). Based on the clinical and functional evidence, the p.Arg396His variant is classified as likely pathogenic for adenylosuccinase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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