ClinVar Miner

Submissions for variant NM_022489.4(INF2):c.1360C>T (p.Leu454Phe) (rs545495465)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235991 SCV000294115 uncertain significance not provided 2016-04-04 criteria provided, single submitter clinical testing The A638T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A638T 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. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter 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 RCV000352897 SCV000385268 likely benign Focal segmental glomerulosclerosis 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000802838 SCV000942683 uncertain significance Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E 2018-10-04 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 454 of the INF2 protein (p.Leu454Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with INF2-related disease. ClinVar contains an entry for this variant (Variation ID: 246526). 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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