ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5896del (p.Ser1966fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV003225690 SCV003921973 uncertain significance Brugada syndrome 1 2022-06-24 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0103 - Loss of function and gain of function are both known mechanisms of disease in this gene. Loss of function is usually associated with Brugada syndrome 1 (MIM#601144) and sick sinus syndrome 1 (SSS) (MIM#608567), whereas gain of function is usually associated with long QT syndrome-3 (LQTS) (MIM#603830). Dilated cardiomyopathy 1E (DCM) (MIM#601154) can be caused by variants with either a loss or gain of function mechanism (PMID: 29798782). (I) 0108 - This gene is associated with both recessive and dominant disease. Most conditions associated with this gene are dominantly inherited; however SSS is caused by biallelic variants (OMIM). (I) 0208 - Variant is predicted to result in an elongated protein. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0710 - Another protein elongation variant comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. A different variant resulting in an elongated protein has been reported as a variant of uncertain significance in association with Brugada syndrome (ClinVar) (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1201 - Heterozygous variant detected in trans with a second pathogenic heterozygous variant (p.(Lys1493del)). (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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