ClinVar Miner

Submissions for variant NM_022489.4(INF2):c.1264C>T (p.Pro422Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001067341 SCV001232398 uncertain significance Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 422 of the INF2 protein (p.Pro422Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. While this variant is present in population databases (rs767748953), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with INF2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; 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.
Illumina Clinical Services Laboratory,Illumina RCV001112035 SCV001269652 benign Focal segmental glomerulosclerosis 5 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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