Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523413 | SCV000618840 | uncertain significance | not provided | 2017-07-05 | criteria provided, single submitter | clinical testing | The c.664 A>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.664 A>C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Multiple in-silico splice prediction models predict that c.664 A>C creates or strengthens a cryptic splice acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of c.664 A>C on splicing in this individual is unknown. If c.664 A>C does not alter splicing, it will result in the N222H missense change. The N222H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Baylor Genetics | RCV001330208 | SCV001521825 | uncertain significance | Dilated cardiomyopathy 1C | 2019-07-03 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
| Invitae | RCV003502536 | SCV004286452 | uncertain significance | Myofibrillar myopathy 4 | 2023-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 222 of the LDB3 protein (p.Asn222His). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 450281). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |