Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000250995 | SCV000320147 | uncertain significance | Cardiovascular phenotype | 2023-05-01 | criteria provided, single submitter | clinical testing | The c.1457+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 16 in the MYBPC3 gene. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort, and in individuals reported to have HCM; however, clinical details were limited in some cases (Lopes LR et al. Heart, 2015 Feb;101:294-301; Ambry internal data). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001246120 | SCV001419458 | uncertain significance | Hypertrophic cardiomyopathy | 2022-06-13 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 264307). This variant has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (PMID: 25351510). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 16 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein. It affects a nucleotide within the consensus splice site. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798756 | SCV002042127 | uncertain significance | Cardiomyopathy | 2021-12-17 | criteria provided, single submitter | clinical testing | |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003338490 | SCV004048343 | uncertain significance | Hypertrophic cardiomyopathy 4 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 16 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (Lopes LR et al). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (Buratti E et al, Zhang MQ et al). The variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as uncertain significance. For these reasons, this variant has been classified as uncertain significance. |