ClinVar Miner

Submissions for variant NM_014845.5(FIG4):c.2095C>T (p.Arg699Cys) (rs764799053)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463654 SCV000546067 uncertain significance Charcot-Marie-Tooth disease type 4 2019-06-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 699 of the FIG4 protein (p.Arg699Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs764799053, ExAC 0.004%). This variant has been observed in an individual affected with amyotropic lateral sclerosis (PMID: 29650794). ClinVar contains an entry for this variant (Variation ID: 407085). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, 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.
Athena Diagnostics Inc RCV000516472 SCV000613295 uncertain significance not specified 2016-09-28 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198716 SCV001369711 uncertain significance Yunis-Varon syndrome 2018-10-30 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.

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