Submissions for variant NM_000257.4(MYH7):c.3726+6C>T

gnomAD frequency: 0.00013  dbSNP: rs377745688

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035863	SCV000059514	likely benign	not specified	2020-09-25	criteria provided, single submitter	clinical testing	The c.3726+C>T variant in MYH7 is classified as likely benign because it has been identified in 0.018% (24/129010) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is located in the 5' splice region; however, computational splice prediction tools do not predict an impact on splicing. Additionally, this variant has been identified in two individuals with HCM with additional variants in another cardiomyopathy gene that were sufficient to explain their observed phenotype (Miller 2013 PMID: 23054336; LMM internal data). ACMG/AMP Criteria applied: BS1, BP4.
GeneDx	RCV001508724	SCV000208429	uncertain significance	not provided	2024-07-17	criteria provided, single submitter	clinical testing	Reported in association with cardiomyopathy and in one individual with HCM who harbored a co-occurring pathogenic variant in the MYBPC3 gene (PMID: 21511876, 23054336, 30847666); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 23054336, 30847666, 21511876)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000549671	SCV000623703	likely benign	Hypertrophic cardiomyopathy	2025-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV003320068	SCV001267468	uncertain significance	Myosin storage myopathy	2018-06-19	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001110079	SCV001267469	uncertain significance	Hypertrophic cardiomyopathy 1	2018-06-19	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001114108	SCV001271943	benign	MYH7-related skeletal myopathy	2018-06-19	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Color Diagnostics, LLC DBA Color Health	RCV001182249	SCV001347637	likely benign	Cardiomyopathy	2019-01-11	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001508724	SCV001715067	uncertain significance	not provided	2020-02-12	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001182249	SCV002042669	likely benign	Cardiomyopathy	2020-01-02	criteria provided, single submitter	clinical testing