Submissions for variant NM_030962.3(SBF2):c.4666T>C (p.Phe1556Leu) (rs189911105)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757738	SCV000886076	uncertain significance	not provided	2018-05-07	criteria provided, single submitter	clinical testing	The SBF2 c.4666T>C; p.Phe1556Leu variant (rs189911105), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.002% (identified on 4 out of 242,768 chromosomes). The phenylalanine at position 1556 is moderately conserved, considering 11 species, and computational analyses of the effects of the p.Phe1556Leu variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Phe1556Leu variant cannot be determined with certainty.
Invitae	RCV000701432	SCV000830233	uncertain significance	Charcot-Marie-Tooth disease type 4	2018-01-11	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine with leucine at codon 1556 of the SBF2 protein (p.Phe1556Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs189911105, ExAC 0.01%). This variant has not been reported in the literature in individuals with SBF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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