ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.1930G>T (p.Gly644Cys) (rs201284198)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227816 SCV000291321 uncertain significance Charcot-Marie-Tooth disease type 2P 2015-11-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 644 of the LRSAM1 protein (p.Gly644Cys). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is present in population databases (rs201284198, ExAC 0.03%) but has not been reported in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000227816 SCV000477230 likely benign Charcot-Marie-Tooth disease type 2P 2018-01-13 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.

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