ClinVar Miner

Submissions for variant NM_030962.3(SBF2):c.3824G>A (p.Arg1275His) (rs150028248)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000215903 SCV000279164 uncertain significance not provided 2018-10-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SBF2 gene. The R1275H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1275H variant is observed in 7/6614 (0.1%) alleles from individuals of Finnish European background and in 35/66716 (0.05%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1275H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably 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.
Illumina Clinical Services Laboratory,Illumina RCV000196586 SCV000375045 uncertain significance Charcot-Marie-Tooth disease type 4 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000196586 SCV000255136 uncertain significance Charcot-Marie-Tooth disease type 4 2019-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1275 of the SBF2 protein (p.Arg1275His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs150028248, 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: 216776). 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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