ClinVar Miner

Submissions for variant NM_001171.6(ABCC6):c.4069C>T (p.Arg1357Trp)

gnomAD frequency: 0.00004  dbSNP: rs63750428
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000499136 SCV001139963 uncertain significance Autosomal recessive inherited pseudoxanthoma elasticum 2023-06-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000132641 SCV001578740 pathogenic not provided 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1357 of the ABCC6 protein (p.Arg1357Trp). This variant is present in population databases (rs63750428, gnomAD 0.03%). This missense change has been observed in individual(s) with pseudoxanthoma elasticum (PMID: 15645653, 16086317, 28912966). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 143119). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCC6 protein function. For these reasons, this variant has been classified as Pathogenic.
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132641 SCV000172592 probable-non-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely benign.
PXE International RCV000499136 SCV000589107 pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2021-03-01 no assertion criteria provided research

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