Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002329874 | SCV002632903 | uncertain significance | Cardiovascular phenotype | 2020-01-17 | criteria provided, single submitter | clinical testing | The p.Y14174H variant (also known as c.42520T>C), located in coding exon 152 of the TTN gene, results from a T to C substitution at nucleotide position 42520. The amino acid change results in tyrosine to histidine at codon 14174, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV004785594 | SCV005399665 | uncertain significance | Hypertrophic cardiomyopathy 9 | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is known mechanism of disease in this gene. In addition, dominant-negative is also a suggested mechanism. (PMID: 25589632). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. Variants in this gene that result in a premature termination codon (PTC) are known to have reduced penetrance in DCM (PMID: 25589632). (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). Affects the last nucleotide of the exon. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 (6 heterozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote). (I) 0508 - In silico predictions for abnormal splicing are conflicting. In silico predictions for abnormal splicing are conflicting. Conflicting silico predictions and uninformative conservation were also identified for this missense variant. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable noncanonical splice variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. Reported as VUS in ClinVar, is otherwise not reported. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |