ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.1897G>A (p.Val633Met)

gnomAD frequency: 0.00002  dbSNP: rs768944520
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001041430 SCV001205047 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 633 of the PLEKHG5 protein (p.Val633Met). This variant is present in population databases (rs768944520, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 839629). 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. 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.
Ambry Genetics RCV004031249 SCV005004417 uncertain significance Inborn genetic diseases 2023-12-13 criteria provided, single submitter clinical testing The c.1897G>A (p.V633M) alteration is located in exon 17 (coding exon 16) of the PLEKHG5 gene. This alteration results from a G to A substitution at nucleotide position 1897, causing the valine (V) at amino acid position 633 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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