ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.430C>G (p.Arg144Gly) (rs1555873985)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV000623989 SCV000740279 likely pathogenic Early infantile epileptic encephalopathy 7 2017-11-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000624475 SCV000742132 likely pathogenic Inborn genetic diseases 2017-01-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Illumina Clinical Services Laboratory,Illumina RCV001249752 SCV001423785 likely pathogenic KCNQ2-Related Disorders 2019-12-06 criteria provided, single submitter clinical testing The KCNQ2 c.430C>G (p.Arg144Gly) variant is a missense variant that has been reported in a heterozygous state in one affected individual with a Rett-like phenotype (Vidal et al. 2019). The affected individual is specifically noted to have psychomotor delay and intellectual disability, but no developmental regression or breathing problems; no additional phenotypes were described. The p.Arg144Gly variant is not found in the Genome Aggregation Database despite good sequence coverage, so the variant is presumed to be rare. Two additional variants at the Arg144 residue have been described in literature, including p.Arg144Gln in an infant who presented with infantile spasms without seizures, global developmental delays, poor eye contact, no speech, inability to walk, and bilateral enlarged kidneys were also noted (Epi4K Consortium et al. 2013). The second variant at the Arg144 residue was identified in an affected individual with intellectual disability, but no additional phenotypes were described (Lelieveld et al. 2016). The p.Arg144Gly variant is located in the third segment of the transmembrane domain (Vidal et al. 2019). Based on the de novo state, absence from population frequency databases, and additional clinical evidence for the Arg144 residue, the p.Arg144Gly variant is classified as likely pathogenic for KCNQ2-related disorders.

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