Submissions for variant NM_030962.3(SBF2):c.5054C>G (p.Ser1685Trp) (rs148468522)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000490082	SCV000576983	uncertain significance	not provided	2017-04-13	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the SBF4 gene. The S1685W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S1685W variant is observed in 14/10390 (0.1%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server)]. The S1685W 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. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to 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
Invitae	RCV000686233	SCV000813742	uncertain significance	Charcot-Marie-Tooth disease type 4	2018-09-24	criteria provided, single submitter	clinical testing	This sequence change replaces serine with tryptophan at codon 1685 of the SBF2 protein (p.Ser1685Trp). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tryptophan. This variant is present in population databases (rs148468522, ExAC 0.1%). This variant has not been reported in the literature in individuals with SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 426520). 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: "Possibly Damaging"; 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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