ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.5555A>C (p.Glu1852Ala)

gnomAD frequency: 0.00001  dbSNP: rs201483184
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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 RCV000707304 SCV000836394 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 2024-05-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1841 of the SCN9A protein (p.Glu1841Ala). This variant is present in population databases (rs201483184, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. ClinVar contains an entry for this variant (Variation ID: 583066). 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 SCN9A protein function with a negative predictive value of 80%. 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.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV001729693 SCV001976728 uncertain significance Channelopathy-associated congenital insensitivity to pain, autosomal recessive 2021-08-10 criteria provided, single submitter clinical testing PM2, PP2, PP3
Ambry Genetics RCV002532868 SCV003665387 uncertain significance Inborn genetic diseases 2022-11-17 criteria provided, single submitter clinical testing The c.5522A>C (p.E1841A) alteration is located in exon 27 (coding exon 26) of the SCN9A gene. This alteration results from a A to C substitution at nucleotide position 5522, causing the glutamic acid (E) at amino acid position 1841 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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