ClinVar Miner

Submissions for variant NM_004281.3(BAG3):c.200A>G (p.Asn67Ser) (rs572036022)

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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 RCV000221765 SCV000271520 uncertain significance not specified 2015-01-26 criteria provided, single submitter clinical testing The p.Asn67Ser variant in BAG3 has not been previously reported in individuals w ith cardiomyopathy but has been identified in 2/67682 European chromosomes and 2 /10572 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs572036022). Computational prediction tools and con servation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.ASn67Ser variant is unc ertain.
Invitae RCV000547161 SCV000650663 uncertain significance Myofibrillar myopathy, BAG3-related; Dilated cardiomyopathy 1HH 2017-03-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 67 of the BAG3 protein (p.Asn67Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs572036022, ExAC 0.02%) but has not been reported in the literature in individuals with a BAG3-related disease. ClinVar contains an entry for this variant (Variation ID: 228456). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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