ClinVar Miner

Submissions for variant NM_004637.6(RAB7A):c.377A>G (p.Lys126Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001202133 SCV001373236 uncertain significance Charcot-Marie-Tooth disease type 2B 2019-10-22 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 126 of the RAB7A protein (p.Lys126Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with peripheral neuropathy (PMID: 26392352). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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