Submissions for variant NC_000011.10:g.47347434del

dbSNP: rs1555122928

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770374	SCV000901815	likely pathogenic	Cardiomyopathy	2015-07-20	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004788039	SCV005400576	pathogenic	Hypertrophic cardiomyopathy 4	2021-05-06	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with hypertrophic cardiomyopathy 4 (MIM#115197). (I) 0108 - This gene is associated with both recessive and dominant disease. Heterozygous variants are frequently reported in adult onset conditions, however recessive inheritance results in a more severe early onset phenotype (OMIM). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic, and have been observed in multiple individuals with hypertrophic cardiomyopathy (HCM) (Decipher). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as likely pathogenic and pathogenic, and observed in multiple individuals with HCM (ClinVar, LOVD, PMID: 30847666, PMID: 23711808, PMID: 24865491, PMID: 22115648). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
All of Us Research Program, National Institutes of Health	RCV004807048	SCV005430059	pathogenic	Hypertrophic cardiomyopathy	2024-03-05	criteria provided, single submitter	clinical testing	The c.897del (p.Lys301Argfs*49) variant in the MYBPC3 gene is located in exon 9, and is predicted to introduce a frameshift and premature translation stop codon. It is predicted to result in an absent or non-functional MYBPC3 protein.This variant has been reported in individuals with hypertrophic cardiomyopathy (PMID:22115648, 20021930). Other loss-of-function variants in this exon have been classified as pathogenic/likely pathogenic in ClinVar (IDs:1764101,181112,1384488). Loss-of-function variants in MYBPC3 gene are known to be pathogenic (PMID: 19574547). ClinVar contains an entry for this variant (ID: 522221). This variant is absent in the general population (gnomAD). Based on this evidence, the c.897del (p.Lys301Argfs*49) variant in the MYBPC3 gene is classified as pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000770374	SCV006061071	pathogenic	Cardiomyopathy	2024-04-08	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 9 of the MYBPC3 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over ten individuals affected with hypertrophic cardiomyopathy (PMID: 22115648, 30847666, 32841044, 33495596). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.