ClinVar Miner

Submissions for variant NM_001085049.3(MRAS):c.13G>A (p.Ala5Thr)

gnomAD frequency: 0.00001  dbSNP: rs767548259
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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 RCV001947417 SCV002133832 uncertain significance not provided 2023-08-10 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 5 of the MRAS protein (p.Ala5Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1367684). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV004785354 SCV005400831 uncertain significance Noonan syndrome 11 criteria provided, single submitter clinical testing The observed missense variant c.13G>A(p.Ala5Thr) in the MRAS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.001% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Ala at position 5 is changed to a Thr changing protein sequence and it might alter its composition and physico- chemical properties. Computational evidence (Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing) predicts conflicting evidence on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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