ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.4516_4524del (p.Gln1506_Pro1508del) (rs397514251)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183165 SCV000235581 pathogenic not provided 2018-06-21 criteria provided, single submitter clinical testing The c.4519_4527delCAGAAGCCC mutation, also referred to as delQKP", in the SCN5A gene has been reported previously in association with LQTS, and was absent from 200 control individuals (Keller D et al., 2003; Shi R et al., 1995). Shi et al. (2010) described a variable phenotype associated with this mutation after identifying c.4519_4527delCAGAAGCCC in a 13 year-old female with a history of first degree AV block, LQTS, and recurrent arrhythmia since birth, who subsequently developed dilated cardiomyopathy. The c.4519_4527delCAGAAGCCC mutation results in the deletion of three amino acids (Glutamine-Lysine-Proline) in the linker region between DIII and DIV in the SCN5A gene (Keller D et al., 2003). This deletion has been also reported as "delKPQ", or p.Lys1505_Glu1507del, when using a different nomenclature (Wang Q et al., 1995). Functional studies reported that this in-frame deletion results in a persistent inward sodium current, consistent with the functional effect reported for other SCN5A mutations (Keller D et al., 2003; Bennett P et al., 1995). In addition, deletion of only the Q1507 residue was found to result in similar functional abnormalities, suggesting the Q1507 residue plays an important role in regulating the sodium ion channel (Keller D et al., 2003)."
Invitae RCV000461009 SCV000545036 pathogenic Brugada syndrome 2019-06-25 criteria provided, single submitter clinical testing This variant, c.4519_4527del, results in the deletion of 3 amino acid(s) of the SCN5A protein (p.Gln1507_Pro1509del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with clinical features of long QT syndrome (LQTS) and observed to segregate with LQTS in a family (PMID: 26467377, 18697752, 23098067, Invitae). ClinVar contains an entry for this variant (Variation ID: 201571). This variant is also known as delQKP1507 1509 or delKPQ in the literature. This variant has been reported to affect SCN5A protein function (PMID: 14654377,18697752, 26022185). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009962 SCV000030183 pathogenic Long QT syndrome 3 1999-08-05 no assertion criteria provided literature only

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