ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.422C>T (p.Thr141Ile)

gnomAD frequency: 0.00009  dbSNP: rs200037593
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001278817 SCV003252596 uncertain significance PHGDH deficiency 2022-10-14 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 141 of the PHGDH protein (p.Thr141Ile). This variant is present in population databases (rs200037593, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PHGDH-related conditions. ClinVar contains an entry for this variant (Variation ID: 990733). 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 RCV002541694 SCV003727851 uncertain significance Inborn genetic diseases 2020-12-03 criteria provided, single submitter clinical testing The c.422C>T (p.T141I) alteration is located in exon 5 (coding exon 5) of the PHGDH gene. This alteration results from a C to T substitution at nucleotide position 422, causing the threonine (T) at amino acid position 141 to be replaced by an isoleucine (I). The p.T141I alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003339575 SCV004049066 uncertain significance Neu-Laxova syndrome 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001278817 SCV004049067 uncertain significance PHGDH deficiency 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001278817 SCV001465859 likely benign PHGDH deficiency 2020-08-10 no assertion criteria provided clinical testing

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