14-23414984-G-A

Variant names:

• chr14-23414984-G-A
• rs565014760
• NM_000257.4:c.5559+11C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000257.4(MYH7):​c.5559+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,604,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 0 publications found

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1S

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• MYH7-related skeletal myopathy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• myopathy, myosin storage, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• myopathy, myosin storage, autosomal dominant

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• congenital myopathy 7A, myosin storage, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ebstein anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hyaline body myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-23414984-G-A is Benign according to our data. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23414984-G-A is described in CliVar as Likely_benign. Clinvar id is 179077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4	c.5559+11C>T		intron_variant	Intron 37 of 39	ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1	c.5559+11C>T		intron_variant	Intron 36 of 38		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4	c.5559+11C>T		intron_variant	Intron 37 of 39	1	NM_000257.4	ENSP00000347507.3
MYH7	ENST00000713768.1	c.5559+11C>T		intron_variant	Intron 37 of 40			ENSP00000519070.1
MYH7	ENST00000713769.1	c.5559+11C>T		intron_variant	Intron 36 of 38			ENSP00000519071.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000205 AC: 5 AN: 244488 AF XY: 0.0000151

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452540 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 723020

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152280 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74456

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jul 18, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

5559+11C>T in intron 37 of MYH7: This variant is not expected to have clinical s ignificance because it is not located within the splice consensus sequence. 555 9+11C>T in intron 37 of MYH7 (allele frequency = not available) -

Hypertrophic cardiomyopathy Benign:1

Jun 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.83
PhyloP100		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs565014760; hg19: chr14-23884193;