ClinVar Miner

Submissions for variant NM_030962.3(SBF2):c.1967G>C (p.Cys656Ser) (rs138120231)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000493165 SCV000615002 uncertain significance not specified 2016-10-31 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763789 SCV000894702 uncertain significance Charcot-Marie-Tooth disease, type 4B2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000766678 SCV000582394 uncertain significance not provided 2018-09-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SBF2 gene. The C656S variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 17/34418 (0.05%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). The C656S 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. In-silico analyses, including protein predictors and evolutionaryconservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000526990 SCV000657941 uncertain significance Charcot-Marie-Tooth disease type 4 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 656 of the SBF2 protein (p.Cys656Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is present in population databases (rs138120231, ExAC 0.04%). This variant has not been reported in the literature in individuals with SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 429748). 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: "Tolerated"; PolyPhen-2: "Probably 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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