ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.1061A>G (p.Lys354Arg) (rs142596580)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656852 SCV000241410 uncertain significance not provided 2018-04-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNJ10 gene. The K354R variant was reported in trans with another KCNJ10 variant (R271C) in an individual with Rett syndrome; however, no additional information was provided (Sajan et al., 2017). The K354R variant is observed in 61/126,624 (0.05%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The K354R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656852 SCV000336762 uncertain significance not provided 2015-11-16 criteria provided, single submitter clinical testing
Invitae RCV000463470 SCV000552195 uncertain significance SeSAME syndrome 2018-05-26 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 354 of the KCNJ10 protein (p.Lys354Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs142596580, ExAC 0.04%). This variant has been reported in an individual affected with Rett syndrome (PMID: 27171548). ClinVar contains an entry for this variant (Variation ID: 205824). 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 variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000656852 SCV000842577 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing

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