ClinVar Miner

Submissions for variant NM_005554.4(KRT6A):c.512A>G (p.Asn171Ser) (rs58556099)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000057010 SCV000321840 pathogenic not provided 2015-12-11 criteria provided, single submitter clinical testing The N171S variant has been published previously in patients with pachyonychia congenita and as a sporadic finding in one patient with the disorder (Smith et al., 2005; Wilson et al., 2011; Liao et al., 2007). It 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. N171S is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position within the 1A domain that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Pathogenic variants at the same codon (N171Y/D/T/K) and missense variants in nearby residues (Q166P, I167S/N, L170F, F174V/I/S/C, S176P) have been reported in the Human Gene Mutation Database in association with Pachyonychia Congenita (Stenson et al., 2014), supporting the functional importance of this region of the protein. As the KRT6A gene has a low rate of benign missense variation, with missense variants being a common mechanism of disease.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057010 SCV000088123 not provided not provided no assertion provided not provided
GeneReviews RCV000128820 SCV000172478 pathogenic Pachyonychia congenita 3 2014-07-24 no assertion criteria provided literature only
OMIM RCV000128820 SCV000189151 pathogenic Pachyonychia congenita 3 2005-10-01 no assertion criteria provided literature only

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