ClinVar Miner

Submissions for variant NM_020631.5(PLEKHG5):c.2233C>A (p.Pro745Thr) (rs756501907)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GenomeConnect, ClinGen RCV000559390 SCV000986941 not provided Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 07/26/2017 by GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000559390 SCV000646024 uncertain significance Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c 2017-01-31 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 745 of the PLEKHG5 protein (p.Pro745Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs756501907, ExAC 0.002%) but has not been reported in the literature in individuals with a PLEKHG5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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