ClinVar Miner

Submissions for variant NM_000171.4(GLRA1):c.1339C>A (p.His447Asn)

gnomAD frequency: 0.00001  dbSNP: rs146481873
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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 RCV001883728 SCV002147225 uncertain significance Hereditary hyperekplexia 2021-04-23 criteria provided, single submitter clinical testing 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 GLRA1 protein function. This sequence change replaces histidine with asparagine at codon 447 of the GLRA1 protein (p.His447Asn). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and asparagine. This variant is present in population databases (rs146481873, ExAC 0.002%). This variant has not been reported in the literature in individuals with GLRA1-related conditions. 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.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV004556089 SCV005045219 likely pathogenic Seizure 2024-05-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV004980853 SCV005591780 uncertain significance Inborn genetic diseases 2024-08-01 criteria provided, single submitter clinical testing The c.1339C>A (p.H447N) alteration is located in exon 9 (coding exon 9) of the GLRA1 gene. This alteration results from a C to A substitution at nucleotide position 1339, causing the histidine (H) at amino acid position 447 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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