ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.374C>T (p.Thr125Met)

gnomAD frequency: 0.00002  dbSNP: rs764618040
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000414985 SCV000492521 likely pathogenic Seizure; Epileptic encephalopathy 2014-06-11 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001196165 SCV001366700 likely pathogenic PHGDH deficiency 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic.
Invitae 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.

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