ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1256G>A (p.Arg419His) (rs777648901)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000549013 SCV000657797 uncertain significance Charcot-Marie-Tooth disease, type 2 2019-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 419 of the LMNA protein (p.Arg419His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs777648901, ExAC 0.03%). This variant has been reported in an individual who died without an established cause (PMID: 27650965). 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. 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001172620 SCV001335683 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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