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NM_001289808.2(CRYAB):c.32G>A (p.Arg11His) AND Dilated cardiomyopathy 1II

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 27, 2024
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:
RCV001089962.13

Allele description [Variation Report for NM_001289808.2(CRYAB):c.32G>A (p.Arg11His)]

NM_001289808.2(CRYAB):c.32G>A (p.Arg11His)

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.32G>A (p.Arg11His)
HGVS:
  • NC_000011.10:g.111911693C>T
  • NG_009824.3:g.17030G>A
  • NG_033080.2:g.3958C>T
  • NM_001289807.1:c.32G>A
  • NM_001289808.2:c.32G>AMANE SELECT
  • NM_001368245.1:c.32G>A
  • NM_001885.3:c.32G>A
  • NP_001276736.1:p.Arg11His
  • NP_001276737.1:p.Arg11His
  • NP_001355174.1:p.Arg11His
  • NP_001876.1:p.Arg11His
  • LRG_407t1:c.32G>A
  • LRG_407t2:c.32G>A
  • LRG_407:g.17030G>A
  • LRG_407p1:p.Arg11His
  • LRG_407p2:p.Arg11His
  • NC_000011.9:g.111782417C>T
  • NG_009824.2:g.17030G>A
  • NG_033080.1:g.3958C>T
  • NM_001885.1:c.32G>A
  • NM_001885.2:c.32G>A
Protein change:
R11H
Links:
dbSNP: rs782809283
NCBI 1000 Genomes Browser:
rs782809283
Molecular consequence:
  • NM_001289807.1:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289808.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368245.1:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001885.3:c.32G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001561066Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 27, 2024) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel mutation in CRYAB associated with autosomal dominant congenital nuclear cataract in a Chinese family.

Chen Q, Ma J, Yan M, Mothobi ME, Liu Y, Zheng F.

Mol Vis. 2009 Jul 10;15:1359-65.

PubMed [citation]
PMID:
19597569
PMCID:
PMC2709425

Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System.

Australian Genomics Health Alliance Acute Care Flagship, Lunke S, Eggers S, Wilson M, Patel C, Barnett CP, Pinner J, Sandaradura SA, Buckley MF, Krzesinski EI, de Silva MG, Brett GR, Boggs K, Mowat D, Kirk EP, Adès LC, Akesson LS, Amor DJ, Ayres S, Baxendale A, Borrie S, Bray A, et al.

JAMA. 2020 Jun 23;323(24):2503-2511. doi: 10.1001/jama.2020.7671.

PubMed [citation]
PMID:
32573669
PMCID:
PMC7312414
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001561066.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 11 of the CRYAB protein (p.Arg11His). 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 cataracts and/or dilated cardiomyopathy (PMID: 19597569, 32573669). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 870393). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CRYAB function (PMID: 21087083, 23194663). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg11 amino acid residue in CRYAB. Other variant(s) that disrupt this residue have been observed in individuals with CRYAB-related conditions (PMID: 26402864), which suggests that this may be a clinically significant amino acid residue. 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.

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

Last Updated: Feb 25, 2025