ClinVar Miner

Submissions for variant NM_001171.6(ABCC6):c.3941G>A (p.Arg1314Gln)

gnomAD frequency: 0.00011  dbSNP: rs63751086
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000454613 SCV000538213 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: LeSaux 2001: reported in 1 compound heterozygote individual (/122) with pseudoxanthoma elasticum. No info about the other mutation
PXE International RCV000499038 SCV000589092 pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2021-03-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001383425 SCV001582566 pathogenic not provided 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1314 of the ABCC6 protein (p.Arg1314Gln). This variant is present in population databases (rs63751086, gnomAD 0.02%). This missense change has been observed in individual(s) with pseudoxanthoma elasticum (PMID: 29722917). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 402332). 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 with a positive predictive value of 95%. This variant disrupts the p.Arg1314 amino acid residue in ABCC6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10835642, 19339160). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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