ClinVar Miner

Submissions for variant NM_001171.6(ABCC6):c.2018T>C (p.Leu673Pro)

gnomAD frequency: 0.00001  dbSNP: rs67470842
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444456 SCV000517453 likely pathogenic not provided 2019-07-30 criteria provided, single submitter clinical testing Published functional studies demonstrate that L673P results in significant misfolding or protein destabilization (Ran et al., 2018); This variant is associated with the following publications: (PMID: 30154241, 12384774, 11536079, 31589614)
Labcorp Genetics (formerly Invitae), Labcorp RCV000444456 SCV003300887 pathogenic not provided 2024-06-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 673 of the ABCC6 protein (p.Leu673Pro). This variant is present in population databases (rs67470842, gnomAD 0.006%). This missense change has been observed in individual(s) with pseudoxanthoma elasticum (PMID: 11536079; Invitae). 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: 379930). 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). For these reasons, this variant has been classified as Pathogenic.
PXE International RCV000499274 SCV000588988 pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2021-03-01 no assertion criteria provided research

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