ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.2T>C (p.Met1Thr)

dbSNP: rs951372478
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001806759 SCV002051138 likely pathogenic PHGDH deficiency 2021-12-15 criteria provided, single submitter clinical testing Variant summary: PHGDH c.2T>C (p.Met1?) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The next alternative downstream in-frame start codon (Met 96) is located at the end of exon 2. Therefore, a severe outcome is predicted. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251114 control chromosomes. To our knowledge, no occurrence of c.2T>C in individuals affected with Phosphoglycerate Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. However, the HGMD database lists at-least one other variant resulting in the same translational impact, namely c.1A>C (p.M1?) that has been associated with a phenotype of Neu-Laxova syndrome, an allelic autosomal recessive disorder with a more severe phenotype that usually results in neonatal death. 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.
Invitae RCV001806759 SCV002152516 pathogenic PHGDH deficiency 2022-02-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1331415). Disruption of the initiator codon has been observed in individual(s) with Neu-Laxova syndrome (PMID: 30838783). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the PHGDH mRNA. The next in-frame methionine is located at codon 96.
Genome-Nilou Lab RCV003339747 SCV004049029 likely pathogenic Neu-Laxova syndrome 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001806759 SCV004049030 likely pathogenic PHGDH deficiency 2023-04-11 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.