ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.569G>A (p.Arg190Gln) (rs142782210)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000218598 SCV000279948 uncertain significance not specified 2017-06-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the LRSAM1 gene. The c.569 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.569 G>A variant is observed in 18/48698 (0.04%) alleles from individuals of European background, including one individual who was homozygous for the variant (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.569 G>A creates a cryptic acceptor site downstream of the natural acceptor site in intron 8 which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown. If the c.569 G>A variant does not effect splicing, it will result in a R190Q missense variant. The R190Q variant is a a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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. Additionally, missense variants in the LRSAM1 gene have not been reported in association with neuropathy (Stenson et al., 2014). 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 RCV000702205 SCV000477208 likely benign Charcot-Marie-Tooth disease type 2P 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.
Invitae RCV000702205 SCV000831049 benign Charcot-Marie-Tooth disease type 2P 2019-12-31 criteria provided, single submitter clinical testing

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