Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497498 | SCV000589431 | uncertain significance | not specified | 2016-06-13 | criteria provided, single submitter | clinical testing | The S180Tvariant has not been published as a pathogenic variant, nor has it been reported as a benign variant toour knowledge. The S180T variant was not observed in approximately 6,500 individuals of Europeanand African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not acommon benign variant in these populations. This substitution occurs at a position that is conservedacross species. Missense variants in nearby residues (T177I, G178R, V186L, N187K, T188N) havebeen reported in the Human Gene Mutation Database in association with hypertrophiccardiomyopathy (HCM) (Stenson et al., 2014). Nevertheless, the S180T variant is a conservativeamino acid substitution, which is not likely to impact secondary protein structure as these residuesshare similar properties. Furthermore, in silico analysis is inconsistent in its predictions as to whetheror not the variant is damaging to the protein structure/function. |
| Ambry Genetics | RCV000619314 | SCV000735481 | uncertain significance | Cardiovascular phenotype | 2016-08-12 | criteria provided, single submitter | clinical testing | The p.S180T variant (also known as c.538T>A), located in coding exon 5 of the MYH7 gene, results from a T to A substitution at nucleotide position 538. The serine at codon 180 is replaced by threonine, an amino acid with some similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001857002 | SCV002135756 | uncertain significance | Hypertrophic cardiomyopathy | 2021-07-27 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 431872). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 180 of the MYH7 protein (p.Ser180Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. |