ClinVar Miner

Submissions for variant NM_033360.4(KRAS):c.436G>T (p.Ala146Ser) (rs121913527)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473918 SCV000552100 likely pathogenic Rasopathy 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 146 of the KRAS protein (p.Ala146Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KRAS-related disease. Family studies have indicated that this variant was not present in the parents of an individual affected with a KRAS-related disease, which suggests that it was de novo in that affected individual (Invitae). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that has been observed to arise de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994878 SCV001148678 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing

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