Submissions for variant NM_000335.5(SCN5A):c.3047C>T (p.Thr1016Met)

gnomAD frequency: 0.00006  dbSNP: rs199473185

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000058545	SCV000637117	likely benign	not provided	2024-12-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000058545	SCV000718211	likely benign	not provided	2020-01-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20129283, 22407026, 15851227)
Color Diagnostics, LLC DBA Color Health	RCV001842326	SCV001339910	likely benign	Cardiac arrhythmia	2019-10-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444520	SCV002752887	likely benign	Cardiovascular phenotype	2022-01-05	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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224133	SCV003920444	uncertain significance	Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10	2021-03-30	criteria provided, single submitter	clinical testing	SCN5A NM_198056.2 exon 17 p.Thr1016Met (c.3047C>T): This variant has not been reported in the literature in association with disease and is present in 0.08% (16/19508) of East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-38622603-G-A). This variant is also present in ClinVar (Variation ID:67774). This variant amino acid Methionine (Met) is present in multiple species including the squirrel monkey, brush-tailed rat, green seaturtle, and painted turtle, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058545	SCV000090065	not provided	not provided		no assertion provided	literature only	This variant has been reported in the following publications (PMID:19841300;PMID:20129283).