ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.1255G>A (p.Gly419Arg)

gnomAD frequency: 0.00006  dbSNP: rs145344767
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520111 SCV000621243 uncertain significance not provided 2023-09-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001271741 SCV003293783 uncertain significance PHGDH deficiency 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 419 of the PHGDH protein (p.Gly419Arg). This variant is present in population databases (rs145344767, gnomAD 0.08%). 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: 452434). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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 RCV002527643 SCV003568715 uncertain significance Inborn genetic diseases 2021-12-02 criteria provided, single submitter clinical testing The c.1255G>A (p.G419R) alteration is located in exon 11 (coding exon 11) of the PHGDH gene. This alteration results from a G to A substitution at nucleotide position 1255, causing the glycine (G) at amino acid position 419 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003338639 SCV004049124 uncertain significance Neu-Laxova syndrome 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001271741 SCV004049125 uncertain significance PHGDH deficiency 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001271741 SCV001453150 likely benign PHGDH deficiency 2019-11-22 no assertion criteria provided clinical testing

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