ClinVar Miner

Submissions for variant NM_004429.4(EFNB1):c.161C>T (p.Pro54Leu) (rs104894801)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478350 SCV000564960 pathogenic not provided 2017-11-14 criteria provided, single submitter clinical testing The P54L variant has been published previously in association with craniofrontonasal syndrome (Wieland et al., 2004; Twigg et al., 2006; Luk et al., 2015). The P54L variant is not observed in large population cohorts (Lek et al., 2016). In vitro functional studies demonstrated that the presence of the P54L variant causes the protein to resist Eph-receptor mediated cell cluster formation and intracellular ephrin-B1 Tyr324 and Tyr329 phosphorylation (Makarov et al., 2010). P54L is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. A likely pathogenic missense variant at the same codon (P54R) has also been reported in the Human Gene Mutation Database in association with craniofrontonasal syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is pathogenic.
OMIM RCV000012474 SCV000032708 pathogenic Craniofrontonasal syndrome 2004-06-01 no assertion criteria provided literature only

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