ClinVar Miner

Submissions for variant NM_015937.6(PIGT):c.1342C>T (p.Arg448Trp) (rs527236031)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000132728 SCV000957008 likely pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 448 of the PIGT protein (p.Arg448Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs527236031, ExAC 0.01%). This variant has been observed to segregate with multiple congenital anomalies-hypotonia-seizures syndrome in a family and has been also found in an unrelated individual with the same pathology (PMID: 24906948, 25943031). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 143194). 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"). 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.
Undiagnosed Diseases Program Translational Research Laboratory,National Institutes of Health RCV000132728 SCV000187657 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 no assertion criteria provided not provided Converted during submission to Pathogenic.
OMIM RCV000132728 SCV000267597 pathogenic Multiple congenital anomalies-hypotonia-seizures syndrome 3 2016-04-25 no assertion criteria provided literature only

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