rs397516096

Variant names:

• chr14-23429039-C-G
• rs397516096
• NM_000257.4:c.1323G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-23429039-C-G
• chr14-23429039-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_000257.4(MYH7):​c.1323G>C​(p.Thr441Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T441T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYH7 NM_000257.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -9.82
• Publications: 3 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 -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-23429039-C-G is Benign according to our data. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-G is described in CliVar as Likely_benign. Clinvar id is 926447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4	c.1323G>C	p.Thr441Thr	synonymous_variant	Exon 14 of 40	ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1	c.1323G>C	p.Thr441Thr	synonymous_variant	Exon 13 of 39		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4	c.1323G>C	p.Thr441Thr	synonymous_variant	Exon 14 of 40	1	NM_000257.4	ENSP00000347507.3
MYH7	ENST00000713768.1	c.1323G>C	p.Thr441Thr	synonymous_variant	Exon 14 of 41			ENSP00000519070.1
MYH7	ENST00000713769.1	c.1323G>C	p.Thr441Thr	synonymous_variant	Exon 13 of 39			ENSP00000519071.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cardiomyopathy Benign:1

Jun 18, 2019

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy Benign:1

Mar 13, 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	0.0040
DANN	Benign	0.59
PhyloP100		-9.8

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: rs397516096; hg19: chr14-23898248;