ClinVar Miner

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

gnomAD frequency: 0.00029  dbSNP: rs142596580
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656852 SCV000241410 uncertain significance not provided 2023-07-12 criteria provided, single submitter clinical testing Observed with a second variant on the opposite allele (in trans) in a patient with Rett syndrome; however, evidence in support of pathogenicity for these variants was not provided in the report (Sajan et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27171548)
Eurofins Ntd Llc (ga) RCV000656852 SCV000336762 uncertain significance not provided 2015-11-16 criteria provided, single submitter clinical testing
Invitae RCV000463470 SCV000552195 uncertain significance EAST syndrome 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 354 of the KCNJ10 protein (p.Lys354Arg). This variant is present in population databases (rs142596580, gnomAD 0.05%). This missense change has been observed in individual(s) 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. 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.
Athena Diagnostics Inc RCV000656852 SCV000842577 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001099388 SCV001255840 uncertain significance Nonsyndromic Hearing Loss, Recessive 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV000463470 SCV001255841 uncertain significance EAST syndrome 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Baylor Genetics RCV001334026 SCV001526761 uncertain significance Autosomal recessive nonsyndromic hearing loss 4 2018-01-16 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002408834 SCV002717266 uncertain significance Inborn genetic diseases 2017-11-29 criteria provided, single submitter clinical testing The p.K354R variant (also known as c.1061A>G), located in coding exon 1 of the KCNJ10 gene, results from an A to G substitution at nucleotide position 1061. The lysine at codon 354 is replaced by arginine, an amino acid with highly similar properties. This alteration was reported in a cohort of subjects with Rett syndrome who underwent exome sequencing (Sajan SA et al. Genet. Med., 2017 Jan;19:13-19). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002503742 SCV002816681 uncertain significance Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome; EAST syndrome 2022-04-27 criteria provided, single submitter clinical testing

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