ClinVar Miner

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

dbSNP: rs796052071
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Total submissions: 5
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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
Invitae 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 2023-09-25 criteria provided, single submitter clinical testing

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