ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.3517G>A (p.Glu1173Lys)

dbSNP: rs542297252
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532749 SCV000648386 uncertain significance Dilated cardiomyopathy 1DD 2022-11-06 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RBM20 protein function. ClinVar contains an entry for this variant (Variation ID: 470612). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. This variant is present in population databases (rs542297252, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1173 of the RBM20 protein (p.Glu1173Lys).
Genetics and Genomics Program, Sidra Medicine RCV001293071 SCV001434053 uncertain significance Primary dilated cardiomyopathy criteria provided, single submitter research
Ambry Genetics RCV002456184 SCV002614646 uncertain significance Cardiovascular phenotype 2023-03-03 criteria provided, single submitter clinical testing The p.E1173K variant (also known as c.3517G>A), located in coding exon 13 of the RBM20 gene, results from a G to A substitution at nucleotide position 3517. The glutamic acid at codon 1173 is replaced by lysine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Genomics Laboratory, Stanford Medicine RCV000532749 SCV004562014 uncertain significance Dilated cardiomyopathy 1DD 2021-04-01 criteria provided, single submitter clinical testing The p.Glu1173Lys variant in the RBM20 gene has not been previously reported in association with disease. • This variant has been identified in 4/22,770 South Asian chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). • Computational tools predict that p.Glu1173Lys variant is deleterious; however, the accuracy of in silico algorithms is limited. • These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Glu1173Lys variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; PP3

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