NM_001289808.2(CRYAB):c.3G>A (p.Met1Ile) AND Dilated cardiomyopathy 1II

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 12, 2023
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:: RCV001358809.14

Allele description [Variation Report for NM_001289808.2(CRYAB):c.3G>A (p.Met1Ile)]

NM_001289808.2(CRYAB):c.3G>A (p.Met1Ile)

Gene:

CRYAB:crystallin alpha B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_001289808.2(CRYAB):c.3G>A (p.Met1Ile)

HGVS:

NC_000011.10:g.111911722C>T
NG_009824.3:g.17001G>A
NG_033080.2:g.3987C>T
NM_001289807.1:c.3G>A
NM_001289808.2:c.3G>AMANE SELECT
NM_001368245.1:c.3G>A
NM_001885.3:c.3G>A
NP_001276736.1:p.Met1Ile
NP_001276737.1:p.Met1Ile
NP_001355174.1:p.Met1Ile
NP_001876.1:p.Met1Ile
LRG_407t1:c.3G>A
LRG_407t2:c.3G>A
LRG_407:g.17001G>A
LRG_407p1:p.Met1Ile
LRG_407p2:p.Met1Ile
NC_000011.9:g.111782446C>T
NG_009824.2:g.17001G>A
NG_033080.1:g.3987C>T
NM_001885.1:c.3G>A
c.3G>A
p.Met1?

Protein change:

M1I

Links:

dbSNP: rs397516686

NCBI 1000 Genomes Browser:

rs397516686

Molecular consequence:

NM_001289807.1:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001289808.2:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001368245.1:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001885.3:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001289807.1:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289808.2:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368245.1:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001885.3:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1II (CMD1II)
Identifiers:: MONDO: MONDO:0014073; MedGen: C3554649; Orphanet: 154; OMIM: 615184

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001554661	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31215171, 33834702, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001554661

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 12, 2023)

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

A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family.

Ma K, Luo D, Tian T, Li N, He X, Rao C, Zhong B, Lu X.

Mol Genet Genomic Med. 2019 Aug;7(8):e825. doi: 10.1002/mgg3.825. Epub 2019 Jun 18.

PubMed [citation]

PMID:: 31215171
PMCID:: PMC6687638

c.3G>A mutation in the CRYAB gene that causes fatal infantile hypertonic myofibrillar myopathy in the Chinese population.

Lu XG, Yu U, Han CX, Mai JH, Liao JX, Hou YQ.

J Integr Neurosci. 2021 Mar 30;20(1):143-151. doi: 10.31083/j.jin.2021.01.267.

PubMed [citation]

PMID:: 33834702

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001554661.5

#	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 affects the initiator methionine of the CRYAB mRNA. The next in-frame methionine is located at codon 68. This variant is present in population databases (rs397516686, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. Disruption of the initiator codon has been observed in individuals with autosomal recessive myofibrillar myopathy (PMID: 31215171, 33834702). ClinVar contains an entry for this variant (Variation ID: 44236). For these reasons, this variant has been classified as Pathogenic.

#	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: Nov 24, 2024

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