NM_000256.3(MYBPC3):c.1805C>T (p.Thr602Ile) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 21, 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:: RCV002516378.2

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1805C>T (p.Thr602Ile)]

NM_000256.3(MYBPC3):c.1805C>T (p.Thr602Ile)

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.1805C>T (p.Thr602Ile)

Other names:

p.T602I:ACC>ATC

HGVS:

NC_000011.10:g.47341230G>A
NG_007667.1:g.16473C>T
NM_000256.3:c.1805C>TMANE SELECT
NP_000247.2:p.Thr602Ile
LRG_386t1:c.1805C>T
LRG_386:g.16473C>T
LRG_386p1:p.Thr602Ile
NC_000011.9:g.47362781G>A

Protein change:

T602I

Links:

dbSNP: rs730880551

NCBI 1000 Genomes Browser:

rs730880551

Molecular consequence:

NM_000256.3:c.1805C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003270425	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 21, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24793961, 31568572, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003270425

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 21, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy.

Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ.

Mayo Clin Proc. 2014 Jun;89(6):727-37. doi: 10.1016/j.mayocp.2014.01.025. Epub 2014 May 1.

PubMed [citation]

PMID:: 24793961
PMCID:: PMC4234122

Targeted panel sequencing in pediatric primary cardiomyopathy supports a critical role of TNNI3.

Kühnisch J, Herbst C, Al-Wakeel-Marquard N, Dartsch J, Holtgrewe M, Baban A, Mearini G, Hardt J, Kolokotronis K, Gerull B, Carrier L, Beule D, Schubert S, Messroghli D, Degener F, Berger F, Klaassen S.

Clin Genet. 2019 Dec;96(6):549-559. doi: 10.1111/cge.13645. Epub 2019 Oct 22.

PubMed [citation]

PMID:: 31568572

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003270425.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 602 of the MYBPC3 protein (p.Thr602Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and left ventricular noncompaction cardiomyopathy (PMID: 24793961, 31568572). ClinVar contains an entry for this variant (Variation ID: 180950). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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