Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822866 | SCV000963688 | uncertain significance | Hypertrophic cardiomyopathy | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 558 of the MYBPC3 protein (p.Ala558Thr). This variant is present in population databases (rs727503198, gnomAD 0.003%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257; Invitae). ClinVar contains an entry for this variant (Variation ID: 164102). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Color Diagnostics, |
RCV001188349 | SCV001355388 | uncertain significance | Cardiomyopathy | 2023-05-05 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 558 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: 27532257). This variant has been identified in 3/280380 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. |
| Ambry Genetics | RCV002399527 | SCV002709479 | uncertain significance | Cardiovascular phenotype | 2022-02-03 | criteria provided, single submitter | clinical testing | The p.A558T variant (also known as c.1672G>A), located in coding exon 18 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 1672. The alanine at codon 558 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy clinical genetic testing cohort; however, clinical details were limited (Walsh R et al. Genet. Med., 2017 Feb;19:192-203). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002483308 | SCV002775644 | uncertain significance | Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 | 2021-09-21 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000151118 | SCV000198887 | uncertain significance | not specified | 2013-02-11 | no assertion criteria provided | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |