Submissions for variant NM_004281.4(BAG3):c.1674G>A (p.Ala558=)

gnomAD frequency: 0.00021  dbSNP: rs142981190

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150188	SCV000197109	likely benign	not specified	2017-05-31	criteria provided, single submitter	clinical testing	p.Ala558Ala in exon 4 of BAG3: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. This variant has been identified in 14/24026 African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org/; dbSNP rs142981190).
Illumina Laboratory Services, Illumina	RCV000317793	SCV000360613	uncertain significance	Dilated cardiomyopathy 1HH	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000374763	SCV000360614	likely benign	Myofibrillar myopathy 6	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001697113	SCV000720924	likely benign	not provided	2020-04-17	criteria provided, single submitter	clinical testing
Invitae	RCV000872394	SCV001014196	likely benign	Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH	2023-12-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002408662	SCV002715211	likely benign	Cardiovascular phenotype	2018-02-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.