ClinVar Miner

Submissions for variant NM_138477.4(CDAN1):c.1763T>C (p.Met588Thr)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002472093 SCV002768497 uncertain significance Anemia, congenital dyserythropoietic, type 1a 2022-03-31 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with congenita; dyserythropoietic anemia, type Ia (MIM#224120). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Marked clinical variability has been seen even in individuals with the same variant (PMID: 20301759, GeneReviews) (I) 0200 - Variant is predicted to result in a missense amino acid change from methionine to threonine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD v2 <0.01 for a recessive condition (33 heterozygotes, 0 homozygotes). (SP) 0309 - Multiple alternative amino acid changes at the same position have been observed in gnomAD (v2) (highest allele count: 1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Labcorp Genetics (formerly Invitae), Labcorp RCV002571479 SCV003027005 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with CDAN1-related conditions. This variant is present in population databases (rs199956917, gnomAD 0.08%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 588 of the CDAN1 protein (p.Met588Thr).
Revvity Omics, Revvity RCV002472093 SCV003829424 uncertain significance Anemia, congenital dyserythropoietic, type 1a 2021-06-28 criteria provided, single submitter clinical testing

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