ClinVar Miner

Submissions for variant NM_032634.4(PIGO):c.2612A>C (p.His871Pro)

gnomAD frequency: 0.00001  dbSNP: rs909488930
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001315307 SCV001505876 uncertain significance Hyperphosphatasia with intellectual disability syndrome 2 2021-05-06 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of PIGO-related conditions (PMID: 28545593, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with proline at codon 871 of the PIGO protein (p.His871Pro). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and proline.
Ambry Genetics RCV002545080 SCV003556287 uncertain significance Inborn genetic diseases 2021-06-25 criteria provided, single submitter clinical testing (Morren, 2017) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003325561 SCV004031500 likely pathogenic not provided 2023-08-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31698102, 34441372, 28545593)

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