ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.3398G>C (p.Gly1133Ala) (rs63750473)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255412 SCV000321364 likely pathogenic not provided 2015-03-17 criteria provided, single submitter clinical testing The G1133A missense change has been reported previously in association with pseudoxanthoma elasticum (PXE) (Pfendner et al., 2007). This 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. The G1133A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across vertebrate species and in silico analyses predict this variant is probably damaging to the protein structure/function. A missense pathogenic variant in this same residue (G1133C), as well as in nearby residues (M1127T, T1130M, R1138W, R1138P, R1128Q, A1139T) have been reported in the Human Gene Mutation Database in association with pseudoxanthoma elasticum (PXE) (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant.
PXE International RCV000499057 SCV000589055 pathogenic Pseudoxanthoma elasticum criteria provided, single submitter research

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