ClinVar Miner

Submissions for variant NM_000032.5(ALAS2):c.1757A>T (p.Tyr586Phe) (rs139596860)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199418 SCV000251131 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing The Y586F variant has previously been reported as heterozygous in a single female patient with moderate congenital erythropoietic porphyria (To-Figueras et al., 2011). Functional analysis of Y586F found that it is assocaited with only a mild gain of function in vitro (To-Figueras et al., 2011). However, the NHLBI Exome Sequencing Project reports Y586F was observed in 31/3835 alleles from individuals of African-American background, indicating it may be a rare, benign variant in this population. The Y586F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Mendelics RCV000990842 SCV001141889 uncertain significance Hereditary sideroblastic anemia 2019-05-28 criteria provided, single submitter clinical testing
GeneReviews RCV000033870 SCV000057778 pathologic Protoporphyria, erythropoietic, X-linked 2013-02-14 no assertion criteria provided curation Converted during submission to Pathogenic.

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