Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035585 | SCV000059235 | uncertain significance | not specified | 2018-05-18 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Glu1128Asp va riant in MYBPC3 has been identified in 1 individual with DCM (Gable 2014) and 1 individual with HCM (LMM data), but has also been identified in 0.017% (21/12346 6) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs375116558). It has been reported in ClinVar (Va riant ID:42710). Computational prediction tools and conservation analysis sugges t that the p.Glu1128Asp variant may not impact the protein, though this informat ion is not predictive enough to rule out pathogenicity. In summary, while the c linical significance of the p.Glu1128Asp variant is uncertain, these data sugges t that it is more likely to be benign. ACMG/AMP criteria applied: BP4. |
Gene |
RCV000766372 | SCV000208168 | uncertain significance | not provided | 2018-05-23 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the MYBPC3 gene. The E1128D variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 21/123466 (0.02%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The E1128D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Invitae | RCV000465772 | SCV000546425 | likely benign | Hypertrophic cardiomyopathy | 2024-01-24 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001188108 | SCV001355080 | uncertain significance | Cardiomyopathy | 2023-02-02 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 1128 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25611685), an individual affected with dilated cardiomyopathy (doi:10.1136/heartjnl-2016-309890.210), and in a case of sudden unexplained death (PMID: 27930701). This variant has been identified in 23/273044 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |