Submissions for variant NM_003098.3(SNTA1):c.1256G>A (p.Arg419His)

gnomAD frequency: 0.00001  dbSNP: rs751302839

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000171104	SCV000223669	uncertain significance	not provided	2014-05-15	criteria provided, single submitter	clinical testing	The R419H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R419H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, the R419H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, no missense mutations in nearby residues have been reported in association with LQTS, indicating this region of the protein may be tolerant of change.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LQT panel(s).
Illumina Laboratory Services, Illumina	RCV000365827	SCV000433487	uncertain significance	Congenital long QT syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000265998	SCV000433488	uncertain significance	Long QT syndrome 12	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV004020043	SCV004954451	uncertain significance	Cardiovascular phenotype	2022-04-06	criteria provided, single submitter	clinical testing	The c.1256G>A (p.R419H) alteration is located in exon 7 (coding exon 7) of the SNTA1 gene. This alteration results from a G to A substitution at nucleotide position 1256, causing the arginine (R) at amino acid position 419 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.