NM_000257.4(MYH7):c.3100-2A>C AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 10, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002320396.3

Allele description [Variation Report for NM_000257.4(MYH7):c.3100-2A>C]

NM_000257.4(MYH7):c.3100-2A>C

Gene:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.3100-2A>C

HGVS:

NC_000014.9:g.23422327T>G
NG_007884.1:g.18335A>C
NM_000257.4:c.3100-2A>CMANE SELECT
NM_001407004.1:c.3100-2A>C
LRG_384:g.18335A>C
NC_000014.8:g.23891536T>G
NC_000014.8:g.23891536T>G
NM_000257.3:c.3100-2A>C

Links:

dbSNP: rs759013925

NCBI 1000 Genomes Browser:

rs759013925

Molecular consequence:

NM_000257.4:c.3100-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407004.1:c.3100-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

Recent activity

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zinc finger protein 528 isoform X3 [Homo sapiens]
zinc finger protein 528 isoform X3 [Homo sapiens]
gi|1034609732|ref|XP_016882854.1|

Protein
Mus musculus RAD51 paralog D (Rad51d), transcript variant 7, non-coding RNA
Mus musculus RAD51 paralog D (Rad51d), transcript variant 7, non-coding RNA
gi|485464624|ref|NR_102718.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002607790	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 10, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29447731, 29517769, 30847666, 33500567 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002607790

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 10, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy.

van Waning JI, Caliskan K, Hoedemaekers YM, van Spaendonck-Zwarts KY, Baas AF, Boekholdt SM, van Melle JP, Teske AJ, Asselbergs FW, Backx APCM, du Marchie Sarvaas GJ, Dalinghaus M, Breur JMPJ, Linschoten MPM, Verlooij LA, Kardys I, Dooijes D, Lekanne Deprez RH, IJpma AS, van den Berg MP, Hofstra RMW, van Slegtenhorst MA, et al.

J Am Coll Cardiol. 2018 Feb 20;71(7):711-722. doi: 10.1016/j.jacc.2017.12.019.

PubMed [citation]

PMID:: 29447731

Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy.

Herkert JC, Abbott KM, Birnie E, Meems-Veldhuis MT, Boven LG, Benjamins M, du Marchie Sarvaas GJ, Barge-Schaapveld DQCM, van Tintelen JP, van der Zwaag PA, Vos YJ, Sinke RJ, van den Berg MP, van Langen IM, Jongbloed JDH.

Genet Med. 2018 Nov;20(11):1374-1386. doi: 10.1038/gim.2018.9. Epub 2018 Mar 8.

PubMed [citation]

PMID:: 29517769

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV002607790.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.3100-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 23 in the MYH7 gene. This variant has been detected in individuals from noncompaction and dilated cardiomyopathy cohorts; however, some cases had other variants in cardiac-related genes (van Waning JI et al. J. Am. Coll. Cardiol., 2018 02;71:711-722; Herkert JC et al. Genet. Med., 2018 11;20:1374-1386; van Lint FHM et al. Neth Heart J. 2019 Jun;27(6):304-309). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of MYH7 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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