ClinVar Miner

Submissions for variant NM_000291.4(PGK1):c.758T>C (p.Ile253Thr)

gnomAD frequency: 0.00001  dbSNP: rs137852534
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000010628 SCV002558056 uncertain significance Glycogen storage disease due to phosphoglycerate kinase 1 deficiency 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with phosphoglycerate kinase 1 deficiency (MIM#30065). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Affected individuals have a highly variable phenotype and age of onset (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from isoleucine to threonine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2) (0 heterozygotes, 0 homozygotes, 2 hemizygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated PGK domain (Pfam). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported in 3 patients with phosphoglycerate kinase 1 deficiency (ClinVar, PMIDs: 2715616, 27848944). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1010 - Functional evidence for this variant is inconclusive. This variant was shown to faintly affect molecular properties and acted similar to wild-type, however these results correlate with the wide spectrum of clinical symptoms (PMID: 22348148). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
OMIM RCV000010628 SCV000030854 pathogenic Glycogen storage disease due to phosphoglycerate kinase 1 deficiency 2006-06-01 no assertion criteria provided literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000010628 SCV001133217 likely pathogenic Glycogen storage disease due to phosphoglycerate kinase 1 deficiency 2019-09-26 no assertion criteria provided clinical testing

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