Submissions for variant NM_000256.3(MYBPC3):c.3489_3490del (p.Gly1164fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
All of Us Research Program, National Institutes of Health	RCV004806853	SCV005429906	pathogenic	Hypertrophic cardiomyopathy	2024-09-12	criteria provided, single submitter	clinical testing	The c.3489_3490del (p.Gly1164Hisfs*4) variant in the MYBPC3 gene introduces a frameshift which creates a premature termination codon. It is predicted to result in an absent or aberrant protein product. Loss-of-function variants in MYBPC3 gene are known to be pathogenic (PMID: 19574547). Other loss-of-function variants in this exon c.3476_3479dup (p.Pro1161fs) and c.3408C>A (p.Tyr1136*), which localize upstream and downstream of this variant, have been classified as pathogenic/likely pathogenic in ClinVar (ID: 42714 and 36611). This variant is absent in the general population. Based on available evidence, this variant is classified as pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV005402213	SCV006062321	pathogenic	Cardiomyopathy	2024-10-15	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 31 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. To our knowledge, this variant has not been reported in individuals affected with MYBPC3-related disorders in the literature. 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.