Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193581 | SCV001362506 | uncertain significance | not specified | 2019-04-08 | criteria provided, single submitter | clinical testing | Variant summary: MYL2 c.181G>C (p.Val61Leu) results in a conservative amino acid change located in the EF-hand domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246260 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.181G>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV002559224 | SCV003343815 | uncertain significance | Hypertrophic cardiomyopathy 10 | 2022-04-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 61 of the MYL2 protein (p.Val61Leu). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 928931). This variant has not been reported in the literature in individuals affected with MYL2-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV004986932 | SCV005451404 | uncertain significance | Cardiovascular phenotype | 2024-12-04 | criteria provided, single submitter | clinical testing | The c.181G>C (p.V61L) alteration is located in exon 4 (coding exon 4) of the MYL2 gene. This alteration results from a G to C substitution at nucleotide position 181, causing the valine (V) at amino acid position 61 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |