ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.3556C>A (p.Leu1186Met)

gnomAD frequency: 0.00005  dbSNP: rs192493052
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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 RCV000203899 SCV000261953 uncertain significance Brugada syndrome 2024-11-13 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1186 of the SCN10A protein (p.Leu1186Met). This variant is present in population databases (rs192493052, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. ClinVar contains an entry for this variant (Variation ID: 220957). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN10A protein function with a positive 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.
Ambry Genetics RCV002453747 SCV002616560 uncertain significance Cardiovascular phenotype 2024-07-07 criteria provided, single submitter clinical testing The p.L1186M variant (also known as c.3556C>A), located in coding exon 20 of the SCN10A gene, results from a C to A substitution at nucleotide position 3556. The leucine at codon 1186 is replaced by methionine, an amino acid with highly similar properties. This variant has been detected in a sudden cardiac arrest cohort; however, details were limited (Giudicessi JR et al. Int J Cardiol, 2018 Nov;270:214-220). This amino acid position is highly 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.
CeGaT Center for Human Genetics Tuebingen RCV003430767 SCV004154209 uncertain significance not provided 2024-08-01 criteria provided, single submitter clinical testing

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