ClinVar Miner

Submissions for variant NM_001289808.2(CRYAB):c.115C>G (p.Pro39Ala)

gnomAD frequency: 0.00003  dbSNP: rs145768025
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000692847 SCV000820692 uncertain significance Dilated cardiomyopathy 1II 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 39 of the CRYAB protein (p.Pro39Ala). This variant is present in population databases (rs145768025, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CRYAB-related conditions. ClinVar contains an entry for this variant (Variation ID: 571646). 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 tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV000764953 SCV000896126 uncertain significance Myofibrillar myopathy 2; Cataract 16 multiple types; Fatal infantile hypertonic myofibrillar myopathy; Dilated cardiomyopathy 1II 2021-09-28 criteria provided, single submitter clinical testing
GeneDx RCV001595033 SCV001829567 uncertain significance not provided 2023-11-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002369867 SCV002624240 uncertain significance Cardiovascular phenotype 2022-10-27 criteria provided, single submitter clinical testing The p.P39A variant (also known as c.115C>G), located in coding exon 1 of the CRYAB gene, results from a C to G substitution at nucleotide position 115. The proline at codon 39 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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