Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780514 | SCV000917829 | uncertain significance | not specified | 2018-06-20 | criteria provided, single submitter | clinical testing | Variant summary: MYH11 c.3314+5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.7e-05 in 244818 control chromosomes (gnomAD). The variant was predominantly observed in the Latino cohort with an allele frequency of 0.00021 (7/33576), which is approximately 168-folds higher than the expected allele frequency for a pathogenic MYH11 variant of 1.3e-06 for Aortopathy. Therefore, suggesting the variant is a benign polymorphism found predominantly in population(s) of Latino origin. To our knowledge, no occurrence of c.3314+5C>T in individuals affected with Aortopathy 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 VUS - possibly benign. |
| Color Diagnostics, |
RCV001190685 | SCV001358252 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2018-11-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001190685 | SCV002611960 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-11-20 | criteria provided, single submitter | clinical testing | The c.3293+5C>T intronic variant results from a C to T substitution 5 nucleotides after coding exon 24 in the MYH11 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002535674 | SCV003517004 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 26 of the MYH11 gene. It does not directly change the encoded amino acid sequence of the MYH11 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs766421052, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 632914). 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 is not likely to affect RNA splicing. 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. |
| All of Us Research Program, |
RCV001190685 | SCV004831777 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2023-07-10 | criteria provided, single submitter | clinical testing |