ClinVar Miner

Submissions for variant NM_000717.5(CA4):c.415A>T (p.Met139Leu) (rs185658468)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000366585 SCV000404390 likely benign Retinitis pigmentosa 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757049 SCV000885132 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing The CA4 c.415A>T; p.Met139Leu variant (rs185658468) is not reported in the medical literature or in gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 324231) and in the Genome Aggregation Database in 0.4% (77/18868 alleles) in the East Asian population and in 0.03% (85/2771900 alleles) overall. The methionine at codon 139 is weakly conserved across species and computational algorithms (PolyPhen-2, SIFT) predict this variant is tolerated. Additionally, this variant occurs in the first nucleotide of the exon and computational algorithms predict there is a small chance this variant alters mRNA splicing (Alamut v.2.11.0). Considering available information, there is insufficient evidence to classify this variant with certainty. Pathogenic CA4 variants are causative for autosomal dominant retinitis pigmentosa (MIM: 600852).
Invitae RCV000757049 SCV001033052 likely benign not provided 2020-11-03 criteria provided, single submitter clinical testing

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