Submissions for variant NM_000030.3(AGXT):c.577del (p.Leu193fs)

dbSNP: rs180177241

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000186398	SCV000486725	likely pathogenic	Primary hyperoxaluria, type I	2016-07-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001238262	SCV001411063	pathogenic	not provided	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu193Phefs*19) in the AGXT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGXT are known to be pathogenic (PMID: 19479957). This variant is present in population databases (rs754693216, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with hyperoxaluria (PMID: 30488096). ClinVar contains an entry for this variant (Variation ID: 204191). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844078	SCV002104105	pathogenic	Primary hyperoxaluria	2022-02-25	criteria provided, single submitter	clinical testing	Variant summary: AGXT c.577delC (p.Leu193PhefsX19) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249482 control chromosomes. c.577delC has been reported in the literature in individuals affected with Primary Hyperoxaluria Type 1 (Williams_2015, Chen_2021). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000186398	SCV002778148	pathogenic	Primary hyperoxaluria, type I	2022-02-24	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000186398	SCV004192828	pathogenic	Primary hyperoxaluria, type I	2024-03-09	criteria provided, single submitter	clinical testing
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000186398	SCV000239748	pathogenic	Primary hyperoxaluria, type I	2014-11-27	no assertion criteria provided	research
Natera, Inc.	RCV000186398	SCV002076465	pathogenic	Primary hyperoxaluria, type I	2020-02-21	no assertion criteria provided	clinical testing
Chinese Inherited Urolithiasis Consortium, The Affiliated Yantai Yuhuangding Hospital of Qingdao University	RCV000186398	SCV005368587	pathogenic	Primary hyperoxaluria, type I	2024-08-26	no assertion criteria provided	clinical testing	Variant_type:truncating/MutationTaster:NONE/CADD:NONE/phyloP:NONE/phastCons:NONE/gnomAD_exome_EastAsian:NONE/ExAC_EastAsian:NONE/dbSNP:NONE