Submissions for variant NM_001134363.3(RBM20):c.2333C>T (p.Ala778Val)

gnomAD frequency: 0.00002  dbSNP: rs397516602

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036964	SCV000060620	uncertain significance	not specified	2012-04-11	criteria provided, single submitter	clinical testing	The Ala778Val variant (RBM20) has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide stron g support for or against an impact to the protein. Additional information is nee ded to fully assess the clinical significance of this variant.
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000853463	SCV000996374	uncertain significance	Hypertrophic cardiomyopathy	2017-04-05	criteria provided, single submitter	research	This variant has been identified as part of our research program. Refer to the 'condition' field for the phenotype of the proband(s) identified with this variant. For further information please feel free to contact us.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001223784	SCV001395948	likely benign	Dilated cardiomyopathy 1DD	2024-09-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003415771	SCV004115279	uncertain significance	RBM20-related disorder	2023-09-07	criteria provided, single submitter	clinical testing	The RBM20 c.2333C>T variant is predicted to result in the amino acid substitution p.Ala778Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-112572488-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486559	SCV004240013	uncertain significance	Cardiomyopathy	2023-03-02	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Stanford Medicine	RCV001223784	SCV004698001	uncertain significance	Dilated cardiomyopathy 1DD	2021-04-16	criteria provided, single submitter	clinical testing	The p.Ala778Val variant in the RBM20 gene has been previously reported in 1 heterozygous individual with HCM (Lopes et al., 2014). This variant has been identified in 3/60,504 European chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational tools predict that the p.Ala778Val variant does not impact protein function; 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.Ala778Val variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; BP4]
Ambry Genetics	RCV004018824	SCV004938865	uncertain significance	Cardiovascular phenotype	2021-01-04	criteria provided, single submitter	clinical testing	The c.2333C>T (p.A778V) alteration is located in exon 9 (coding exon 9) of the RBM20 gene. This alteration results from a C to T substitution at nucleotide position 2333, causing the alanine (A) at amino acid position 778 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.