Submissions for variant NM_000048.4(ASL):c.1060C>T (p.Gln354Ter)

dbSNP: rs367543005

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078007	SCV000225991	pathogenic	not provided	2016-05-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000078007	SCV000238699	pathogenic	not provided	2016-09-09	criteria provided, single submitter	clinical testing	p.Q354* CAG>TAG c.1060C>T nonsense variant in the ASL gene was identified in the homozygous state in 14 of 28 patients from Saudi Arabia who were diagnosed with argininosuccinic aciduria (ASA) after being detected on MS/MS newborn screening (Al-Sayed et al., 2005). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Counsyl	RCV000020415	SCV000485605	pathogenic	Argininosuccinate lyase deficiency	2016-07-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000020415	SCV000694148	pathogenic	Argininosuccinate lyase deficiency	2016-05-05	criteria provided, single submitter	clinical testing	Variant summary: The c.1060C>T variant results in a premature termination codon, predicted to cause a truncated or absent ASL protein, which is a commonly known mechanism for disease. One in-silico tool predicts damaging outcome for this variant. 4/5 splice prediction tools predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions are not confirmed by experimental studies.This variant is not found in 116646 control chromosomes. This variant has been reported in many affected individuals as a founder mutation in the Saudi population (Al-Sayed_JIMD_2005). In addition, multiple clinical laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	RCV000020415	SCV000891477	pathogenic	Argininosuccinate lyase deficiency	2017-12-30	criteria provided, single submitter	curation
Revvity Omics, Revvity	RCV000020415	SCV002019529	pathogenic	Argininosuccinate lyase deficiency	2021-10-06	criteria provided, single submitter	clinical testing
Invitae	RCV000020415	SCV003440599	pathogenic	Argininosuccinate lyase deficiency	2023-05-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln354*) in the ASL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASL are known to be pathogenic (PMID: 2263616, 24166829). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with argininosuccinic aciduria (PMID: 16435180). ClinVar contains an entry for this variant (Variation ID: 21253). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003914857	SCV004730921	pathogenic	ASL-related condition	2024-01-03	criteria provided, single submitter	clinical testing	The ASL c.1060C>T variant is predicted to result in premature protein termination (p.Gln354*). This variant was reported to be causative for argininosuccinic aciduria (Al-Sayed et al. 2005. PubMed ID: 16435180; AlTassan et al. 2018. PubMed ID: 29326055). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in ASL are expected to be pathogenic. This variant is interpreted as pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000020415	SCV004805173	pathogenic	Argininosuccinate lyase deficiency	2024-03-17	criteria provided, single submitter	research
GeneReviews	RCV000020415	SCV000040815	not provided	Argininosuccinate lyase deficiency		no assertion provided	literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000020415	SCV001133190	pathogenic	Argininosuccinate lyase deficiency	2019-09-26	no assertion criteria provided	clinical testing
OMIM	RCV000020415	SCV002026474	pathogenic	Argininosuccinate lyase deficiency	2021-11-22	no assertion criteria provided	literature only