Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000151367 | SCV000199357 | uncertain significance | not specified | 2016-05-23 | criteria provided, single submitter | clinical testing | The p.Arg40Lys variant in MYL2 has been reported in 1 Caucasian newborn and 2 Ca ucasian adults with HCM (Berge 2014, LMM data). It has not been identified in la rge population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summa ry, the clinical significance of the p.Arg40Lys variant is uncertain. |
| Gene |
RCV000766478 | SCV000208854 | uncertain significance | not provided | 2022-05-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25611685, 24111713, 27532257) |
| Labcorp Genetics |
RCV000464490 | SCV000549153 | uncertain significance | Hypertrophic cardiomyopathy 10 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 40 of the MYL2 protein (p.Arg40Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ​hypertrophic cardiomyopathy (PMID: 24111713, 27532257; Invitae). ClinVar contains an entry for this variant (Variation ID: 164481). 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 tolerated. 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. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000624062 | SCV000740465 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2016-11-29 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000464490 | SCV000894705 | uncertain significance | Hypertrophic cardiomyopathy 10 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Genetics and Genomics Program, |
RCV001293059 | SCV001434041 | uncertain significance | Hypertrophic cardiomyopathy | criteria provided, single submitter | research | ||
| Ambry Genetics | RCV002345474 | SCV002640820 | uncertain significance | Cardiovascular phenotype | 2021-08-18 | criteria provided, single submitter | clinical testing | The p.R40K variant (also known as c.119G>A), located in coding exon 3 of the MYL2 gene, results from a G to A substitution at nucleotide position 119. The arginine at codon 40 is replaced by lysine, an amino acid with highly similar properties. This variant has been reported in individuals with hypertrophic cardiomyopathy (HCM) and in HCM genetic testing cohorts; however, clinical details have been limited (Wang J et al. Eur J Heart Fail, 2014 Sep;16:950-7; Berge KE et al. Clin Genet, 2014 Oct;86:355-60; Walsh R et al. Genet Med, 2017 02;19:192-203). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |