ClinVar Miner

Submissions for variant NM_001482.3(GATM):c.1022C>T (p.Pro341Leu)

dbSNP: rs1889422661
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel, ClinGen RCV001332014 SCV003852684 uncertain significance Arginine:glycine amidinotransferase deficiency 2023-01-24 reviewed by expert panel curation The NM_001482.3:c.1022C>T variant in GATM is a missense variant predicted to cause substitution of proline by leucine at amino acid 341 (p.Pro341Leu). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.476 which is neither above nor below the thresholds predicting a damaging (>0.75) or benign (<0.15) impact on AGAT function. There is a ClinVar entry for this variant (Variation ID: 917496). To our knowledge, this variant has not been reported in an individual with phenotypic features of AGAT deficiency. It has been reported as a single heterozygous variant segregating in a family autosomal dominant renal Fanconi syndrome and kidney failure (PMID: 29654216). However, classification with respect to this alternative disorder is outside the scope of this curation. There is a ClinVar entry for this variant (Variation ID: 917496). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for AGAT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP on January 24, 2023).
Baylor Genetics RCV001332014 SCV001524197 uncertain significance Arginine:glycine amidinotransferase deficiency 2019-02-14 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease causing [PMID 29654216]
Fulgent Genetics, Fulgent Genetics RCV002483940 SCV002791731 uncertain significance Arginine:glycine amidinotransferase deficiency; Fanconi renotubular syndrome 1 2022-04-30 criteria provided, single submitter clinical testing
OMIM RCV001174512 SCV001337651 pathogenic Fanconi renotubular syndrome 1 2020-06-11 no assertion criteria provided literature only

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