ClinVar Miner

Submissions for variant NM_003722.5(TP63):c.1681T>G (p.Cys561Gly) (rs121908843)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001067605 SCV001232673 likely pathogenic TP63-Related Spectrum Disorders 2019-01-29 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 561 of the TP63 protein (p.Cys561Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with ankyloblepharon-ectodermal dysplasia-clefting syndrome (PMID: 11159940). This variant is also known as c.1546T>G, p.Cys526Gly in the literature. ClinVar contains an entry for this variant (Variation ID: 6536). This variant has been reported to affect TP63 protein function (PMID:21615690). 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. This variant disrupts the p.Cys561 amino acid residue in TP63. Other variant(s) that disrupt this residue have been observed in individuals with TP63-related conditions (PMID:11159940, 19793345), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000006910 SCV000027106 pathogenic Hay-Wells syndrome of ectodermal dysplasia 2001-02-01 no assertion criteria provided literature only

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