ClinVar Miner

Submissions for variant NM_022489.4(INF2):c.1962G>C (p.Glu654Asp)

gnomAD frequency: 0.00001  dbSNP: rs1378876029
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000649965 SCV000771802 uncertain significance Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E 2017-09-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 654 of the INF2 protein (p.Glu654Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with INF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002422391 SCV002721459 uncertain significance Inborn genetic diseases 2021-03-04 criteria provided, single submitter clinical testing The p.E654D variant (also known as c.1962G>C), located in coding exon 10 of the INF2 gene, results from a G to C substitution at nucleotide position 1962. The glutamic acid at codon 654 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and aspartic acid is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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