ClinVar Miner

Submissions for variant NM_001289808.2(CRYAB):c.343del (p.Ser115fs) (rs281865142)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183328 SCV000235760 pathogenic not provided 2017-04-05 criteria provided, single submitter clinical testing The c.343delT pathogenic variant in the CRYAB gene was reported as a homozygous pathogenic variant in one infant with myofibrillar myopathy (Forrest K et al., 2011). This infant presented with feeding difficulties and respiratory distress requiring ventilation, however her echocardiogram was normal. Her parents were heterozygous carriers of the mutation, and were asymptomatic at the time of the publication. This variant causes a shift in reading frame starting at codon Serine 115, changing it to a Proline, and creating a premature stop codon at position 14 of the new reading frame, denoted p.Ser115ProfsX14. This variant is expected to result in an abnormal, truncated protein product. In summary, c.343delT in the CRYAB gene is interpreted as a pathogenic variant.
Invitae RCV000694268 SCV000822704 pathogenic Dilated cardiomyopathy 1II 2020-08-09 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CRYAB gene (p.Ser115Profs*14). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt 15 residues and delete the last 46 amino acids of the CRYAB protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in individuals affected with myofibrillar myopathy (PMID: 21130652, 27226619). ClinVar contains an entry for this variant (Variation ID: 38963). Experimental studies have shown that this frameshift mutation leads to insolubility of CRYAB protein (PMID: 21130652, 27226619). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000183328 SCV000862831 likely pathogenic not provided 2018-08-08 criteria provided, single submitter clinical testing
GeneReviews RCV000032215 SCV000055817 pathologic Alpha-B crystallinopathy 2012-10-29 no assertion criteria provided curation Converted during submission to Pathogenic.

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