Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482502 | SCV000573162 | uncertain significance | not provided | 2017-02-08 | criteria provided, single submitter | clinical testing | The I988S variant has not been publishedas pathogenic or been reported as benign to our knowledge. It is not observed in large population cohorts (Lek et al.,2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I988S variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity,charge, size and/or other properties. Moreover, this substitution occurs at a position that is conserved throughmammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damagingto the protein structure/function. |
| Invitae | RCV002525934 | SCV003034526 | uncertain significance | Hypertrophic cardiomyopathy | 2022-07-21 | criteria provided, single submitter | clinical testing | 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: 423459). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 988 of the MYH7 protein (p.Ile988Ser). |