Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000414985 | SCV000492521 | likely pathogenic | Seizure; Epileptic encephalopathy | 2014-06-11 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV001196165 | SCV001366700 | likely pathogenic | PHGDH deficiency | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. |
Labcorp Genetics |
RCV001196165 | SCV002157648 | uncertain significance | PHGDH deficiency | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 125 of the PHGDH protein (p.Thr125Met). This variant is present in population databases (rs764618040, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of PHGDH-related conditions (PMID: 29286531). ClinVar contains an entry for this variant (Variation ID: 373899). 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. 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. |
Ambry Genetics | RCV002524662 | SCV003639152 | uncertain significance | Inborn genetic diseases | 2022-10-13 | criteria provided, single submitter | clinical testing | The c.374C>T (p.T125M) alteration is located in exon 4 (coding exon 4) of the PHGDH gene. This alteration results from a C to T substitution at nucleotide position 374, causing the threonine (T) at amino acid position 125 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |