ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.177G>C (p.Lys59Asn)

gnomAD frequency: 0.00001  dbSNP: rs1487584331
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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 RCV001998288 SCV002259812 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2021-08-19 criteria provided, single submitter clinical testing 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. This sequence change replaces lysine with asparagine at codon 59 of the OPTN protein (p.Lys59Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 21074290). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").
Ambry Genetics RCV002398037 SCV002711236 uncertain significance Inborn genetic diseases 2023-07-31 criteria provided, single submitter clinical testing The c.177G>C (p.K59N) alteration is located in exon 3 (coding exon 2) of the OPTN gene. This alteration results from a G to C substitution at nucleotide position 177, causing the lysine (K) at amino acid position 59 to be replaced by an asparagine (N). The alteration is rare in population databases: _x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the c.177G>C alteration was observed in 0.002% (5/251,012) of total alleles studied. This amino acid position is well conserved in available vertebrate species. The alteration is predicted deleterious by in silico models:_x000D_ _x000D_ The p.K59N alteration is predicted to be probably damaging by Polyphen and deleterious by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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