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

dbSNP: rs121913527

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000473918	SCV000552100	likely pathogenic	RASopathy	2018-08-18	criteria provided, single submitter	clinical testing	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. 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. 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). 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. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000994878	SCV001148678	uncertain significance	not provided	2017-09-01	criteria provided, single submitter	clinical testing