Submissions for variant NM_020937.4(FANCM):c.3058T>A (p.Leu1020Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003523900	SCV004249663	uncertain significance	Fanconi anemia	2023-11-07	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1020 of the FANCM protein (p.Leu1020Met). This variant is present in population databases (rs747842904, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx	RCV004763699	SCV005372023	uncertain significance	not provided	2023-07-25	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge