Submissions for variant NM_006623.4(PHGDH):c.403C>G (p.Arg135Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002904904	SCV003260055	uncertain significance	PHGDH deficiency	2021-11-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 135 of the PHGDH protein (p.Arg135Gly). This variant is present in population databases (rs267606949, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PHGDH-related conditions. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg135T amino acid residue in PHGDH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19235232, 26610677). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.