ClinVar Miner

Submissions for variant NM_005157.6(ABL1):c.677A>G (p.Tyr226Cys)

dbSNP: rs1060499547
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000445576 SCV000485092 pathogenic Congenital heart disease; Failure to thrive; Abnormal skeletal morphology 2016-12-11 criteria provided, single submitter clinical testing This variant has been found four times in our laboratory in individuals with heart defects, skeletal anomalies, and failure to thrive. In two families, it co-segregated with disease, and it arose de novo in a third.
GeneDx RCV001796027 SCV002032419 pathogenic not provided 2021-10-22 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant leads to a gain of function with increased ABL kinase activity (Wang et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28288113)
MGZ Medical Genetics Center RCV000496944 SCV002581798 likely pathogenic Congenital heart defects and skeletal malformations syndrome 2022-08-22 criteria provided, single submitter clinical testing
3billion RCV000496944 SCV005904148 pathogenic Congenital heart defects and skeletal malformations syndrome 2023-10-05 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 28288113, 28288113). In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.67 (>=0.6, sensitivity 0.68 and specificity 0.92)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000374795 /PMID: 28288113 /3billion dataset). The variant has been previously reported as de novo in a similarly affected individual (PMID: 28288113). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
OMIM RCV000496944 SCV000586799 pathogenic Congenital heart defects and skeletal malformations syndrome 2017-08-02 no assertion criteria provided literature only

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