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NM_139343.3(BIN1):c.433C>T (p.Arg145Cys) AND Myopathy, centronuclear, 2

Germline classification:
Likely pathogenic (3 submissions)
Last evaluated:
Mar 10, 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:
RCV000754844.7

Allele description [Variation Report for NM_139343.3(BIN1):c.433C>T (p.Arg145Cys)]

NM_139343.3(BIN1):c.433C>T (p.Arg145Cys)

Gene:
BIN1:bridging integrator 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q14.3
Genomic location:
Preferred name:
NM_139343.3(BIN1):c.433C>T (p.Arg145Cys)
HGVS:
  • NC_000002.12:g.127069010G>A
  • NG_012042.1:g.43279C>T
  • NM_001320632.2:c.433C>T
  • NM_001320633.2:c.433C>T
  • NM_001320634.1:c.361C>T
  • NM_001320640.2:c.433C>T
  • NM_001320641.2:c.433C>T
  • NM_001320642.1:c.352C>T
  • NM_004305.4:c.433C>T
  • NM_139343.3:c.433C>TMANE SELECT
  • NM_139344.3:c.433C>T
  • NM_139345.3:c.433C>T
  • NM_139346.3:c.433C>T
  • NM_139347.3:c.433C>T
  • NM_139348.3:c.433C>T
  • NM_139349.3:c.433C>T
  • NM_139350.3:c.433C>T
  • NM_139351.3:c.433C>T
  • NP_001307561.1:p.Arg145Cys
  • NP_001307562.1:p.Arg145Cys
  • NP_001307563.1:p.Arg121Cys
  • NP_001307569.1:p.Arg145Cys
  • NP_001307570.1:p.Arg145Cys
  • NP_001307571.1:p.Arg118Cys
  • NP_004296.1:p.Arg145Cys
  • NP_647593.1:p.Arg145Cys
  • NP_647594.1:p.Arg145Cys
  • NP_647595.1:p.Arg145Cys
  • NP_647596.1:p.Arg145Cys
  • NP_647597.1:p.Arg145Cys
  • NP_647598.1:p.Arg145Cys
  • NP_647599.1:p.Arg145Cys
  • NP_647600.1:p.Arg145Cys
  • NP_647601.1:p.Arg145Cys
  • LRG_873t1:c.433C>T
  • LRG_873:g.43279C>T
  • LRG_873p1:p.Arg145Cys
  • NC_000002.11:g.127826586G>A
  • NM_004305.3:c.433C>T
Protein change:
R118C; ARG145CYS
Links:
OMIM: 601248.0006; dbSNP: rs1249621033
NCBI 1000 Genomes Browser:
rs1249621033
Molecular consequence:
  • NM_001320632.2:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320633.2:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320634.1:c.361C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320640.2:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320641.2:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001320642.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004305.4:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139343.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139344.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139345.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139346.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139347.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139348.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139349.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139350.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139351.3:c.433C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Myopathy, centronuclear, 2 (CNM2)
Synonyms:
MYOTUBULAR MYOPATHY, AUTOSOMAL RECESSIVE
Identifiers:
MONDO: MONDO:0009709; MedGen: C0410204; Orphanet: 169186; OMIM: 255200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000882724OMIM
no assertion criteria provided
Pathogenic
(Feb 8, 2019)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000930063SIB Swiss Institute of Bioinformatics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jan 8, 2019)
unknowncuration

PubMed (2)
[See all records that cite these PMIDs]

SCV002252306Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Mar 10, 2023)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedcuration
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

A Roma founder BIN1 mutation causes a novel phenotype of centronuclear myopathy with rigid spine.

Cabrera-Serrano M, Mavillard F, Biancalana V, Rivas E, Morar B, Hernández-Laín A, Olive M, Muelas N, Khan E, Carvajal A, Quiroga P, Diaz-Manera J, Davis M, Ávila R, Domínguez C, Romero NB, Vílchez JJ, Comas D, Laing NG, Laporte J, Kalaydjieva L, Paradas C.

Neurology. 2018 Jul 24;91(4):e339-e348. doi: 10.1212/WNL.0000000000005862. Epub 2018 Jun 27.

PubMed [citation]
PMID:
29950440
PMCID:
PMC6070382
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000882724.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

For discussion of the c.433C-T transition (c.433C-T, NM_139343) in the BIN1 gene, resulting in an arg145-to-cys (R145C) substitution, that was found in compound heterozygous state in Spanish Roma patients with centronuclear myopathy (CNM2; 255200) by Cabrera-Serrano et al. (2018), see 601248.0005.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From SIB Swiss Institute of Bioinformatics, SCV000930063.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

This variant is interpreted as a Likely pathogenic for Myopathy, centronuclear, 2 autosomal recessive. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM1 : Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation. PP1 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:29950440). PM3 : For recessive disorders, detected in trans with a pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002252306.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant is present in population databases (no rsID available, gnomAD 0.0009%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BIN1 protein function. ClinVar contains an entry for this variant (Variation ID: 617682). This missense change has been observed in individual(s) with autosomal recessive centronuclear myopathy (PMID: 29950440). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 145 of the BIN1 protein (p.Arg145Cys).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024