Submissions for variant NM_000335.5(SCN5A):c.3628ATC[1] (p.Ile1211del)

dbSNP: rs794728920

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183162	SCV000235578	pathogenic	not provided	2013-08-22	criteria provided, single submitter	clinical testing	c.3634_3636delATC: p.Ile1212del (I1212del) in exon 20 of the SCN5A gene (NM_198056.2). The normal sequence with the bases that are deleted in braces is: CATC{ATC}TTCA. The c.3634_3636delATC mutation in the SCN5A gene has been reported previously as a novel mutation in one individual tested for Long QT syndrome and Brugada syndrome (Kapplinger J et al., 2009; Kapplinger J et al., 2010). Mutations in nearby residues (Ser1218Ile, Ser1219Asn) have been reported in association with Brugada syndrome, further supporting the functional importance of this region of the protein. Furthermore, c.3634_3636delATC 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. In summary, c.3634_3636delATC in the SCN5A gene is interpreted as a disease-causing mutation. The variant is found in POSTMORTEM panel(s).
Ambry Genetics	RCV004658981	SCV005157699	uncertain significance	Cardiovascular phenotype	2024-03-29	criteria provided, single submitter	clinical testing	The c.3634_3636delATC variant (also known as p.I1212del) is located in coding exon 19 of the SCN5A gene. This variant results from an in-frame ATC deletion at nucleotide positions 3634 to 3636. This results in the in-frame deletion of an isoleucine at codon 1212. This alteration has been reported in a long QT syndrome cohort; however, clinical details were limited (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this alteration remains unclear.