ClinVar Miner

Submissions for variant NM_001171.6(ABCC6):c.2294G>A (p.Arg765Gln)

gnomAD frequency: 0.00006  dbSNP: rs67561842
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PXE International RCV000023275 SCV000589001 pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2021-03-01 criteria provided, single submitter research
CeGaT Center for Human Genetics Tuebingen RCV001090336 SCV001245827 pathogenic not provided 2017-01-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001090336 SCV002023919 pathogenic not provided 2023-02-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001090336 SCV002238673 pathogenic not provided 2023-10-29 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 765 of the ABCC6 protein (p.Arg765Gln). This variant is present in population databases (rs67561842, gnomAD 0.02%). This missense change has been observed in individuals with pseudoxanthoma elasticum (PMID: 12673275, 30805891). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30337). 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%. Experimental studies have shown that this missense change affects ABCC6 function (PMID: 30154241). This variant disrupts the p.Arg765 amino acid residue in ABCC6. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18157818; Invitae). 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.
OMIM RCV000023275 SCV000044566 pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2010-01-01 no assertion criteria provided literature only
OMIM RCV000023276 SCV000044567 pathogenic Arterial calcification, generalized, of infancy, 2 2010-01-01 no assertion criteria provided literature only

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