ClinVar Miner

Submissions for variant NM_015937.6(PIGT):c.514C>T (p.Arg172Cys)

gnomAD frequency: 0.00002  dbSNP: rs778531326
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698476 SCV000827142 uncertain significance Multiple congenital anomalies-hypotonia-seizures syndrome 3 2022-07-22 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of PIGT-congenital disorder of glycosylation (PMID: 32220244, 32404165). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 576072). This variant is present in population databases (rs778531326, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 172 of the PIGT protein (p.Arg172Cys).
Mendelics RCV000698476 SCV001141241 likely pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001726308 SCV001962385 likely pathogenic not provided 2021-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001726308 SCV004036780 likely pathogenic not provided 2023-03-29 criteria provided, single submitter clinical testing Observed multiple times with a second variant on the opposite allele (in trans) in unrelated patients with epilepsy and developmental delay in the published literature (Jiao et al., 2020; Issa et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36177944, 32220244, 32404165)
OMIM RCV000698476 SCV003926533 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2023-05-24 no assertion criteria provided literature only

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