Submissions for variant NM_000257.4(MYH7):c.1000-7C>T

gnomAD frequency: 0.00006  dbSNP: rs200129563

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035692	SCV000059343	likely benign	not specified	2015-06-25	criteria provided, single submitter	clinical testing	c.1000-7C>T in intron 11 of MYH7: This variant is not expected to have clinical significance because a C>T change at this position does not diverge from the spl ice consensus sequence and is therefore unlikely to impact splicing. It has been identified in 2/10376 of African chromosomes and 2/11550 of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs200129563).
Illumina Laboratory Services, Illumina	RCV003320039	SCV000386269	likely benign	Myosin storage myopathy	2019-10-22	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000265960	SCV000386271	likely benign	Dilated cardiomyopathy 1S	2019-10-22	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000323421	SCV000386272	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094072	SCV000386273	likely benign	Hypertrophic cardiomyopathy 1	2019-10-22	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000288259	SCV000386274	likely benign	MYH7-related skeletal myopathy	2019-10-22	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000380268	SCV000557961	likely benign	Hypertrophic cardiomyopathy	2024-01-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727084	SCV000705507	uncertain significance	not provided	2017-01-23	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769463	SCV000900857	uncertain significance	Cardiomyopathy	2023-06-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769463	SCV001360094	likely benign	Cardiomyopathy	2019-01-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000727084	SCV001886059	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000727084	SCV002822125	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	MYH7: BP4
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	RCV000380268	SCV001430820	uncertain significance	Hypertrophic cardiomyopathy	2019-11-26	no assertion criteria provided	research	The MYH7 c.1000-7C>T variant has not been previously reported in literature, but has been seen identified in 2 HCM cases by another laboratory (ClinVar SCV000059343). The variant is present at an elevated frequency in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a proband with HCM, no family history of disease or sudden cardiac death. The proband also carries 2 other variants (TNNT2 c.571-7G>A & TNNT2 Arg278His). In summary, based on rarity in the general population, and our limited familial data, we classify MYH7 c.1000-7C>T as a variant of "uncertain significance".