ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.386C>T (p.Ala129Val) (rs876657747)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688851 SCV000816477 uncertain significance Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2018-09-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 129 of the BAG3 protein (p.Ala129Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 228457). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000214731 SCV000271521 uncertain significance not specified 2015-04-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala129Val var iant in BAG3 has not been previously reported in individuals with cardiomyopathy or in large population studies. Alanine (Ala) at position 129 is not conserved in mammals or evolutionarily distant species and at least 2 mammals (gibbon, bus hbaby) carry a valine (Val) at this position, raising the possibility that this change may be tolerated. In summary, while the clinical significance of the p.Al a129Val variant is uncertain, these data suggest that it is more likely to be be nign.

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