ClinVar Miner

Submissions for variant NM_030962.3(SBF2):c.479G>T (p.Cys160Phe) (rs1214507322)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519383 SCV000621062 uncertain significance not provided 2017-09-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SBF2 gene. The C160F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The C160F variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The C160F 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. This substitution occurs at a position that is conserved in mammals; however, Phenylalanine is observed at this position in evolution. 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 RCV001052163 SCV001216360 uncertain significance Charcot-Marie-Tooth disease type 4 2019-05-21 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 160 of the SBF2 protein (p.Cys160Phe). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SBF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 452269). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001108274 SCV001265495 uncertain significance Charcot-Marie-Tooth disease, type 4B2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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