Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194321 | SCV001363760 | uncertain significance | not specified | 2019-10-29 | criteria provided, single submitter | clinical testing | Variant summary: LDB3 c.1805A>C (p.Tyr602Ser) results in a non-conservative amino acid change located in the Zinc finger, LIM-type domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251496 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1805A>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001243566 | SCV001416734 | uncertain significance | Myofibrillar myopathy 4 | 2019-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with serine at codon 602 of the LDB3 protein (p.Tyr602Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. The LDB3 gene has multiple clinically relevant transcripts. The p.Tyr602Ser variant occurs in alternate transcript NM_007078.2, which corresponds to c.*18718A>C in NM_001080116.1, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDB3-related conditions. 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: "Not Available"; Align-GVGD: "Class C65"). 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. |
Ambry Genetics | RCV002411730 | SCV002710842 | uncertain significance | Cardiovascular phenotype | 2022-03-17 | criteria provided, single submitter | clinical testing | The p.Y602S variant (also known as c.1805A>C), located in coding exon 10 of the LDB3 gene, results from an A to C substitution at nucleotide position 1805. The tyrosine at codon 602 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |