ClinVar Miner

Submissions for variant NM_022489.4(INF2):c.1147G>A (p.Val383Met) (rs780689756)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493332 SCV000582466 uncertain significance not provided 2017-05-15 criteria provided, single submitter clinical testing The V383M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V383M variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function.
Invitae RCV001205939 SCV001377221 uncertain significance Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E 2019-09-17 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 383 of the INF2 protein (p.Val383Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. The frequency data for this variant in the population databases is considered 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. ClinVar contains an entry for this variant (Variation ID: 429808). 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 methionine 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.

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