ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.1301T>C (p.Ile434Thr) (rs763653491)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462412 SCV000547796 uncertain significance Fanconi anemia 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 434 of the FANCM protein (p.Ile434Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs763653491, ExAC 0.1%) but has not been reported in the literature in individuals with a FANCM-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 threonine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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