Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040019 | SCV000063710 | uncertain significance | not specified | 2012-05-11 | criteria provided, single submitter | clinical testing | The Ala7105Gly variant in TTN has not been previously reported, but has been det ected in 1 individual with DCM tested by our laboratory. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIF T) do not provide strong support for or against an impact to the protein. Compu tational tools predict that this variant may affect splicing, but additional stu dies are needed to further investigate this. In summary, additional information is needed to fully assess the clinical significance of the Ala7105Gly variant. |
| Gene |
RCV000766986 | SCV000618236 | uncertain significance | not provided | 2017-10-16 | criteria provided, single submitter | clinical testing | The A8032G variant of uncertain significance in the TTN gene has not been published as a pathogenic or benignvariant to our knowledge. The A8032G variant is not observed at a significant frequency in large population cohorts(Lek et al., 2016). This variant could be functionally significant at the mRNA or protein level. At the mRNA level,several in silico splicing models predict that this variant probably affects splicing by creating a strong cryptic donorsite upstream of the natural donor site for intron 84. However, in the absence of functional mRNA studies, thephysiological consequence of this variant cannot be determined. At the protein level, the A8032G variant is aconservative amino acid substitution that occurs at a position that is not conserved across species. In silico analysis isinconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |