ClinVar Miner

Submissions for variant NM_030962.4(SBF2):c.3163A>G (p.Ile1055Val)

gnomAD frequency: 0.00004  dbSNP: rs142891020
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000544537 SCV000657951 uncertain significance Charcot-Marie-Tooth disease type 4 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1055 of the SBF2 protein (p.Ile1055Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs142891020, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. 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. 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757736 SCV000886074 uncertain significance not provided 2017-11-09 criteria provided, single submitter clinical testing The p.Ile1055Val variant (rs142891020) has not been reported in the medical literature, and it is not listed in gene-specific variant databases. The p.Ile1055Val variant is listed in the Genome Aggregation Database (gnomAD) browser with an overall allele frequency of 0.002% (identified in 5 out of 246,176 chromosomes). The isoleucine at codon 1055 is moderately conserved considering 11 species (Alamut software v2.10.0), and computational analyses predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen2: benign, MutationTaster: disease causing). Based on the available information, the clinical significance of the p.Ile1055Val variant cannot be determined with certainty.
Illumina Laboratory Services, Illumina RCV001114471 SCV001272358 uncertain significance Charcot-Marie-Tooth disease type 4B2 2018-01-12 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.
GeneDx RCV000757736 SCV002044141 uncertain significance not provided 2021-06-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Ambry Genetics RCV004024391 SCV004945707 uncertain significance Inborn genetic diseases 2023-09-22 criteria provided, single submitter clinical testing The c.3163A>G (p.I1055V) alteration is located in exon 25 (coding exon 25) of the SBF2 gene. This alteration results from a A to G substitution at nucleotide position 3163, causing the isoleucine (I) at amino acid position 1055 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV000757736 SCV005412291 uncertain significance not provided 2024-07-01 criteria provided, single submitter clinical testing PM2

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