Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000151208 | SCV000199043 | uncertain significance | not specified | 2013-11-25 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Arg1987X va riant in MYH14 has not been previously reported in individuals with hearing loss or in large population studies. This nonsense variant leads to a premature term ination codon at position 1987 which is 50 amino acid positions upstream of the canonical termination codon. However, the truncation occurs within 50 nucleotide s of the terminal exon-exon junction, and nonsense mediated decay may not occur (Zhang 1998). Therefore, the impact of the variant on the normal function of the protein cannot be predicted. In summary, the clinical significance of this vari ant cannot be determined with certainty; however due to the fact that the varian t is predicted to result in a truncated protein, we would lean towards a more li kely pathogenic role. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000151208 | SCV004121767 | uncertain significance | not specified | 2023-10-17 | criteria provided, single submitter | clinical testing | Variant summary: MYH14 c.5836C>T (p.Arg1946X) results in a premature termination codon which is predicted to cause a truncation of the encoded protein, but is not expected to result in nonsense mediated decay. The variant was absent in 249144 control chromosomes (gnomAD). To our knowledge, no occurrence of c.5836C>T in individuals affected with Autosomal Dominant Deafness and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |