ClinVar Miner

Submissions for variant NM_000422.3(KRT17):c.280C>T (p.Arg94Cys) (rs58730926)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000056513 SCV000321827 pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing The R94C variant has been published previously in association with steatocystoma multiplex and pachyonychia congenita type 2 (Covello et al., 1998; Liu et al., 2015; Cammarata-Scalisi et al., 2015). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. R94C is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the rod and coil 1A domain that is conserved across species, is intolerant of change, and where many pathogenic variants cluster. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in the same residue (R94S/G/P/H) and in nearby residues (L91P, N92D/H/S, L95P/Q, Y98D, L99P) have been reported in the Human Gene Mutation Database in association with steatocystoma multiplex and pachyonychia congenita type 2 (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we consider this variant to be pathogenic.
OMIM RCV000015694 SCV000035959 pathogenic Steatocystoma multiplex 1998-09-01 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056513 SCV000087624 not provided not provided no assertion provided not provided
OMIM RCV000114415 SCV000148347 pathogenic Pachyonychia congenita 2 1998-09-01 no assertion criteria provided literature only

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