Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000004071 | SCV000698713 | pathogenic | PHGDH deficiency | 2017-07-23 | criteria provided, single submitter | clinical testing | Variant summary: The PHGDH c.1468G>A (p.Val490Met) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO and MutationTaster not captured due to low reliability index). This variant was found in 13/123042 control chromosomes at a frequency of 0.0001059, which does not exceed the estimated maximal expected allele frequency of a pathogenic PHGDH variant (0.0026352). The variant has been reported in the homozygous state in numerousffected individuals, and functional studies showed the variant to result in significantly reduced enzyme activity in transfected cells as well as patient fibroblasts (Klomp_2000, Pind_2002). In addition, one reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Invitae | RCV000004071 | SCV000951673 | pathogenic | PHGDH deficiency | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 490 of the PHGDH protein (p.Val490Met). This variant is present in population databases (rs121907987, gnomAD 0.2%). This missense change has been observed in individuals with phosphoglycerate dehydrogenase deficiency (PMID: 11055895, 11751922). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3867). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PHGDH protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects PHGDH function (PMID: 11055895, 11751922). For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000004071 | SCV001135397 | pathogenic | PHGDH deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Rady Children's Institute for Genomic Medicine, |
RCV000004071 | SCV001984849 | pathogenic | PHGDH deficiency | 2020-06-05 | criteria provided, single submitter | clinical testing | This variant has been reported in several individuals affected with phosphoglycerate dehydrogenase deficiency and was found to segregate with the disease in related individuals (PMID: 11055895, 11751922). Functional studies have shown that this change disrupts PHGDH enzymatic activity in vitro (PMID: 11055895, 11751922). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.00014 (40/281324) and thus is presumed to be rare. In silico analyses are suggestive of deleterious effect of the c.1468G>A (p.Val490Met) variant on protein function. Based on the available evidence, the c.1468G>A (p.Val490Met) variant is classified as Pathogenic. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV002251869 | SCV002523267 | likely pathogenic | See cases | 2019-10-02 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS3, PS4, PP1, PP3 |
Fulgent Genetics, |
RCV002482824 | SCV002790572 | pathogenic | PHGDH deficiency; Neu-Laxova syndrome 1 | 2022-03-19 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003338378 | SCV004049138 | likely pathogenic | Neu-Laxova syndrome 1 | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000004071 | SCV004049139 | likely pathogenic | PHGDH deficiency | 2023-04-11 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004071 | SCV000024237 | pathogenic | PHGDH deficiency | 2000-12-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000004071 | SCV001461724 | pathogenic | PHGDH deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |