Submissions for variant NM_000166.6(GJB1):c.224G>A (p.Arg75Gln) (rs863224972)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000201183	SCV000255687	pathogenic	X-linked hereditary motor and sensory neuropathy	2013-03-04	criteria provided, single submitter	clinical testing
Invitae	RCV000691748	SCV000819538	pathogenic	Charcot-Marie-Tooth Neuropathy X	2019-10-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 75 of the GJB1 protein (p.Arg75Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with X-linked Charcot-Marie-Tooth disease (CMTX) (PMID: 8829637, 9272161, 10093067, 12402337). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217167). This variant has been reported to affect GJB1 protein function (PMID: 12460545, 19369543, 23209285). 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. For these reasons, this variant has been classified as Pathogenic.

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