ClinVar Miner

Submissions for variant NM_153704.5(TMEM67):c.638G>A (p.Arg213His) (rs770605718)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542172 SCV000634633 uncertain significance Joubert syndrome; Meckel-Gruber syndrome 2017-07-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 213 of the TMEM67 protein (p.Arg213His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs770605718, ExAC 0.02%). This variant has not been reported in the literature in individuals with a TMEM67-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 and their clinical significance is uncertain. In summary, this variant has uncertain impact on TMEM67 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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