Submissions for variant NM_000030.3(AGXT):c.662_664del (p.Ser221del)

dbSNP: rs796052071

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000186401	SCV000239751	pathogenic	Primary hyperoxaluria, type I	2023-10-27	criteria provided, single submitter	clinical testing	Liver AGT activity <10%. ACMG: PS3 PM2 PP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265672	SCV002547491	likely pathogenic	Primary hyperoxaluria	2022-05-12	criteria provided, single submitter	clinical testing	Variant summary: AGXT c.662_664delCCT (p.Ser221del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 251102 control chromosomes (gnomAD). c.662_664delCCT has been reported in the literature in homozygous and compound heterozygous individuals affected with Primary Hyperoxaluria Type 1 (van der Hoeven_2012, Poloni_2016, Birtel_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000186401	SCV002802193	likely pathogenic	Primary hyperoxaluria, type I	2021-10-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002517833	SCV003525304	pathogenic	not provided	2023-09-05	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 204194). This variant disrupts a region of the AGXT protein in which other variant(s) (p.Ser221Pro) have been observed in individuals with AGXT-related conditions (PMID: 25629080). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of primary hyperoxaluria type 1 (PMID: 22844106, 26759051, 35149915; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant, c.662_664del, results in the deletion of 1 amino acid(s) of the AGXT protein (p.Ser221del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs796052071, gnomAD 0.006%).
Baylor Genetics	RCV000186401	SCV004194605	likely pathogenic	Primary hyperoxaluria, type I	2024-02-20	criteria provided, single submitter	clinical testing
Chinese Inherited Urolithiasis Consortium, The Affiliated Yantai Yuhuangding Hospital of Qingdao University	RCV000186401	SCV005368590	likely pathogenic	Primary hyperoxaluria, type I	2024-08-26	no assertion criteria provided	clinical testing	Variant_type:codonmutation/MutationTaster:NONE/CADD:NONE/phyloP:NONE/phastCons:NONE/gnomAD_exome_EastAsian:NONE/ExAC_EastAsian:NONE/dbSNP:NONE