ClinVar Miner

Submissions for variant NM_001171.5(ABCC6):c.3412C>T (p.Arg1138Trp) (rs28939701)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255802 SCV000321365 pathogenic not provided 2017-01-09 criteria provided, single submitter clinical testing The R1138W missense pathogenic variant in the ABCC6 gene has been reported previously in the homozygous finding or heterozygous with a second variant in association with pseudoxanthoma elasticum (PXE) (Ringpfiel et al., 2000; Miksch et al., 2005; Pfendner et al., 2007; Hesse et al., 2010). It was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. The R1138W variant 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 that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in at the same codon (R1138Q, R1138P) and in nearby residues (G1133C/A, A1139T) have been reported in the Human Gene Mutation Database in association with PXE (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R1138W as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000762960 SCV000893398 pathogenic Pseudoxanthoma elasticum; Pseudoxanthoma elasticum, forme fruste; Generalized arterial calcification of infancy 2 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000006949 SCV000027145 pathogenic Pseudoxanthoma elasticum 2001-08-01 no assertion criteria provided literature only
PXE International RCV000006949 SCV000589056 pathogenic Pseudoxanthoma elasticum no assertion criteria provided research

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