rs373301620

Variant names:

• chr14-23431752-C-A
• rs373301620
• NM_000257.4:c.639+9G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23431752-C-A
• chr14-23431752-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000257.4(MYH7):​c.639+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,258 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 0.0000066 (0 hom., cov: 33)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0600
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-23431752-C-A is Benign according to our data. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23431752-C-A is described in CliVar as Likely_benign. Clinvar id is 3008127.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4	c.639+9G>T		intron_variant	Intron 7 of 39	ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1	c.639+9G>T		intron_variant	Intron 6 of 38		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4	c.639+9G>T		intron_variant	Intron 7 of 39	1	NM_000257.4	ENSP00000347507.3
MYH7	ENST00000713768.1	c.639+9G>T		intron_variant	Intron 7 of 40			ENSP00000519070.1
MYH7	ENST00000713769.1	c.639+9G>T		intron_variant	Intron 6 of 38			ENSP00000519071.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251482 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertrophic cardiomyopathy Benign:1

Apr 08, 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	-0.82
CADD	Benign	3.1
DANN	Benign	0.57
PhyloP100		-0.060

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: rs373301620; hg19: chr14-23900961;