ClinVar Miner

Submissions for variant NM_176787.5(PIGN):c.283C>T (p.Arg95Trp)

dbSNP: rs558341655
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000514477 SCV000514115 uncertain significance not provided 2016-02-20 criteria provided, single submitter clinical testing The R95W variant in the PIGN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R95W variant was not observed in approximately 6100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R95W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R95W as a variant of uncertain significance.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000514477 SCV000606863 pathogenic not provided 2017-10-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000623425 SCV000740783 uncertain significance Inborn genetic diseases 2015-03-28 criteria provided, single submitter clinical testing
Invitae RCV000796566 SCV000936085 likely pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 95 of the PIGN protein (p.Arg95Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with an abnormality of the nervous system and/or PIGN-related conditions (PMID: 26633542, 35179230, 35468813). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 378361). 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 expected to disrupt PIGN protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000796566 SCV001523871 likely pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 2020-01-23 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Mendelics RCV000796566 SCV002518857 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 1 2022-05-04 criteria provided, single submitter clinical testing

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