ClinVar Miner

Submissions for variant NM_003098.3(SNTA1):c.287G>C (p.Gly96Ala)

gnomAD frequency: 0.00014  dbSNP: rs766925398
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656979 SCV000223655 uncertain significance not provided 2024-03-19 criteria provided, single submitter clinical testing Identified in a patient with a history of recurrent arrhythmias and incidental finding of fenestrated membrane overlying left atrial appendage (PMID: 33070394); this patient also harbored a pathogenic variant in the LMNA gene; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33070394)
Eurofins Ntd Llc (ga) RCV000656979 SCV000332551 uncertain significance not provided 2015-07-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000540961 SCV000627698 uncertain significance Long QT syndrome 2025-01-26 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 96 of the SNTA1 protein (p.Gly96Ala). This variant is present in population databases (rs766925398, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 190907). 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 not expected to disrupt SNTA1 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781872 SCV000920251 uncertain significance not specified 2018-07-31 criteria provided, single submitter clinical testing Variant summary: SNTA1 c.287G>C (p.Gly96Ala) results in a non-conservative amino acid change located in the Pleckstrin homology domain and PDZ domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 144728 control chromosomes (gnomAD). The observed variant frequency is more than 10-fold above the estimated maximal expected allele frequency for a pathogenic variant in SNTA1 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.287G>C in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as a VUS possibly benign variant.
Mayo Clinic Laboratories, Mayo Clinic RCV000656979 SCV001713850 uncertain significance not provided 2019-10-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002433740 SCV002751255 likely benign Cardiovascular phenotype 2023-07-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002492708 SCV002785298 uncertain significance Long QT syndrome 12 2021-08-23 criteria provided, single submitter clinical testing

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