Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002514704 | SCV003523348 | uncertain significance | PHGDH deficiency | 2022-07-04 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 140 of the PHGDH protein (p.Gly140Arg). This variant is present in population databases (rs587777770, gnomAD 0.007%). This missense change has been observed in individual(s) with Neu-Laxova syndrome (PMID: 24836451, 26960553). ClinVar contains an entry for this variant (Variation ID: 139534). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Genomic Medicine Center of Excellence, |
RCV002514704 | SCV004801211 | likely pathogenic | PHGDH deficiency | 2024-03-14 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002514704 | SCV005887734 | pathogenic | PHGDH deficiency | 2025-01-21 | criteria provided, single submitter | clinical testing | Variant summary: PHGDH c.418G>A (p.Gly140Arg) results in a non-conservative amino acid change located in the D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain (IPR006140) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251474 control chromosomes. c.418G>A has been reported in the literature in multiple homozygous individuals affected with clinical features of Phosphoglycerate Dehydrogenase Deficiency (Shaheen_2014, El-Hattab_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26960553, 24836451, 30214071). ClinVar contains an entry for this variant (Variation ID: 139534). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000128433 | SCV000172114 | pathogenic | Neu-Laxova syndrome 1 | 2014-06-05 | no assertion criteria provided | literature only | |
| Genomic Medicine Center of Excellence, |
RCV000171157 | SCV000221353 | likely pathogenic | not provided | flagged submission | research |