ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.1941G>A (p.Met647Ile)

dbSNP: rs1227129126
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693247 SCV000821107 uncertain significance Benign neonatal seizures 2023-08-30 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 647 of the KCNQ3 protein (p.Met647Ile). This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. ClinVar contains an entry for this variant (Variation ID: 571968). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNQ3 protein function. 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.
Baylor Genetics RCV001329911 SCV001521470 uncertain significance Seizures, benign familial neonatal, 2 2019-03-28 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002406582 SCV002719295 uncertain significance Inborn genetic diseases 2019-09-22 criteria provided, single submitter clinical testing The p.M647I variant (also known as c.1941G>A), located in coding exon 15 of the KCNQ3 gene, results from a G to A substitution at nucleotide position 1941. The methionine at codon 647 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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