ClinVar Miner

Submissions for variant NM_003098.2(SNTA1):c.770C>G (p.Ala257Gly) (rs56157422)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171774 SCV000050786 likely benign Long QT syndrome 2013-06-24 criteria provided, single submitter research
Ambry Genetics RCV000247418 SCV000318140 likely benign Cardiovascular phenotype 2018-05-16 criteria provided, single submitter clinical testing Other strong data supporting benign classification;Subpopulation frequency in support of benign classification
Invitae RCV000171774 SCV000563491 likely benign Long QT syndrome 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000191018 SCV000605231 uncertain significance Long QT syndrome 12 2018-12-17 criteria provided, single submitter clinical testing The SNTA1 c.770C>G; p.Ala257Gly variant (rs56157422) is reported in the literature in individuals affected with long QT syndrome (Wu 2008), but has also been reported in in carriers with a slightly longer QTc interval (Ghouse 2015). Additionally, this variant is found in healthy controls when found in combination with p.Pro74Leu, and functional studies suggest that the p.Pro74Leu variant rescues the in vitro channel activity defect of the p.Ala257Gly variant (Cheng 2011). This variant is reported in ClinVar (Variation ID: 191548), and is found in the non-Finnish European population with an allele frequency of 0.34% (442/128,676 alleles, including 3 homozygotes) in the Genome Aggregation Database. The alanine at codon 257 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to conflicting information, the clinical significance of the p.Ala257Gly variant is uncertain at this time. References: Cheng J et al. Alpha1-syntrophin mutations identified in sudden infant death syndrome cause an increase in late cardiac sodium current. Circ Arrhythm Electrophysiol. 2009 Dec;2(6):667-76. Cheng J et al. LQTS-associated mutation A257G in a1-syntrophin interacts with the intragenic variant P74L to modify its biophysical phenotype. Cardiogenetics. 2011 Oct 25;1(1). pii: 136. Ghouse J et al. Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval. Eur Heart J. 2015 Oct 1;36(37):2523-9. Wu G et al. Alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circ Arrhythm Electrophysiol. 2008 Aug;1(3):193-201.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000191018 SCV000743435 likely benign Long QT syndrome 12 2016-07-08 criteria provided, single submitter clinical testing
Mendelics RCV000990299 SCV001141232 uncertain significance Long QT syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
OMIM RCV000191018 SCV000245994 pathogenic Long QT syndrome 12 2008-08-01 no assertion criteria provided literature only

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