ClinVar Miner

Submissions for variant NM_001005373.4(LRSAM1):c.1757A>G (p.Tyr586Cys)

gnomAD frequency: 0.00004  dbSNP: rs768302528
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001224255 SCV001396442 uncertain significance Charcot-Marie-Tooth disease axonal type 2P 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 586 of the LRSAM1 protein (p.Tyr586Cys). This variant is present in population databases (rs768302528, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 952194). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRSAM1 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002402699 SCV002714331 uncertain significance Inborn genetic diseases 2021-04-02 criteria provided, single submitter clinical testing The p.Y586C variant (also known as c.1757A>G), located in coding exon 21 of the LRSAM1 gene, results from an A to G substitution at nucleotide position 1757. The tyrosine at codon 586 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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