ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1573A>T (p.Ile525Leu)

dbSNP: rs755925068
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001880241 SCV002196561 uncertain significance Fanconi anemia 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 525 of the FANCA protein (p.Ile525Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs755925068, ExAC 0.02%). This variant has not been reported in the literature in individuals with FANCA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV005340739 SCV006001907 uncertain significance Inborn genetic diseases 2025-02-08 criteria provided, single submitter clinical testing The p.I525L variant (also known as c.1573A>T), located in coding exon 17 of the FANCA gene, results from an A to T substitution at nucleotide position 1573. The isoleucine at codon 525 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Natera, Inc. RCV001277945 SCV001464930 uncertain significance Fanconi anemia complementation group A 2020-08-13 no assertion criteria provided clinical testing

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