ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.4591C>T (p.Pro1531Ser) (rs142875103)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000215884 SCV000271484 uncertain significance not specified 2015-09-22 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro1531Ser va riant in ABCC9 has not been previously reported in individuals with cardiomyopat hy, but has been identified in 6/10386 of African chromosomes by the Exome Aggre gation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs142875103). Pro line (Pro) at position 1531 is not conserved in mammals or evolutionarily distan t species and >15 birds and reptiles carry a serine (Ser) at this position, rais ing the possibility that this change may be tolerated. In summary, while the cli nical significance of the p.Pro1531Ser variant is uncertain, these data suggest that it is more likely to be benign.
Invitae RCV000474358 SCV000551691 uncertain significance Dilated cardiomyopathy 1O 2018-09-19 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1531 of the ABCC9 protein (p.Pro1531Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs142875103, ExAC 0.06%). This variant has not been reported in the literature in individuals with a ABCC9-related disease. ClinVar contains an entry for this variant (Variation ID: 228426). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on ABCC9 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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