ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3242G>A (p.Arg1081Gln) (rs140079523)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539421 SCV000630142 uncertain significance Progressive sclerosing poliodystrophy 2017-02-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1081 of the POLG protein (p.Arg1081Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs140079523, ExAC 0.01%). This variant has been reported in two siblings affected with Alpers-like syndrome (PMID: 21550804). It has also been observed in an individual affected with muscle weakness and ataxia, however a second variant was not identified in this individual (PMID: 21550804). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735364 SCV000854518 uncertain significance Plagiocephaly; Global developmental delay; Visual impairment; Cortical visual impairment; Generalized hypotonia; Hypsarrhythmia; Postnatal microcephaly; Posterior plagiocephaly; Epileptic encephalopathy; Infantile spasms; Mild microcephaly criteria provided, single submitter clinical testing
Mendelics RCV000539421 SCV001139677 pathogenic Progressive sclerosing poliodystrophy 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000995412 SCV001149556 likely pathogenic not provided 2016-05-01 criteria provided, single submitter clinical testing

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