NM_000256.3(MYBPC3):c.2995-1G>A AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000158205.4

Allele description [Variation Report for NM_000256.3(MYBPC3):c.2995-1G>A]

NM_000256.3(MYBPC3):c.2995-1G>A

Gene:

MYBPC3:myosin binding protein C3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_000256.3(MYBPC3):c.2995-1G>A

HGVS:

NC_000011.10:g.47333753C>T
NG_007667.1:g.23950G>A
NM_000256.3:c.2995-1G>AMANE SELECT
LRG_386t1:c.2995-1G>A
LRG_386:g.23950G>A
NC_000011.9:g.47355304C>T

Links:

dbSNP: rs730880584

NCBI 1000 Genomes Browser:

rs730880584

Molecular consequence:

NM_000256.3:c.2995-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000208140	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (May 24, 2017)	germline	clinical testing	Citation Link,
SCV004226847	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25132132, 27532257, 33190526, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000208140

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(May 24, 2017)

germline

clinical testing

Citation Link,

SCV004226847

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 27, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy.

Wang J, Wang Y, Zou Y, Sun K, Wang Z, Ding H, Yuan J, Wei W, Hou Q, Wang H, Liu X, Zhang H, Ji Y, Zhou X, Sharma RK, Wang D, Ahmad F, Hui R, Song L.

Eur J Heart Fail. 2014 Sep;16(9):950-7. doi: 10.1002/ejhf.144. Epub 2014 Jul 31.

PubMed [citation]

PMID:: 25132132

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000208140.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Although the c.2995-1 G>A variant has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge, this variant destroys the canonical splice acceptor site in intron 28 and is predicted to cause abnormal gene splicing. The variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site mutations in the MYBPC3 gene have been reported in association with HCM. In summary, c.2995-1 G>A in the MYBPC3 gene is interpreted as a disease-causing variant

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226847.1

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

Description

PS4_moderate, PVS1

#	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		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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