ClinVar Miner

Submissions for variant NM_000165.5(GJA1):c.681A>T (p.Glu227Asp) (rs875989815)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703618 SCV000832526 uncertain significance Oculodentodigital dysplasia, autosomal recessive 2018-03-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 227 of the GJA1 protein (p.Glu227Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with erythrokeratodermia variabilis et progressiva without features of oculodental dysplasia and the variant is de novo in one of these individuals (PMID: 25398053). ClinVar contains an entry for this variant (Variation ID: 203468). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
OMIM RCV000185624 SCV000238536 pathogenic Erythrokeratodermia variabilis et progressiva 3 2015-06-01 no assertion criteria provided literature only

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