Important Variant Information for SCN5A
Submitted by: Ping Yang and Andrew Wooldridge (PAT)
Reviewed by: Reviewed
Submitted date: Dec 21, 2006
There are Three Important Variants for SCN5A.
| Gene HGNC Name: | SCN5A |
|---|---|
| Variant Summary: | R34C was observed with a minor allelic frequency of 9.2% among blacks and 1.7% among Hispanics [PMID: 15851227]. The frequency of this common nonsynonymous coding region polymorphism was no different between patients with drug-induced long QT syndrome and control subjects, 3% versus 3% [PMID: 11997281]. |
| Key PubMed IDs: | 15851227, 11997281, 15992732 |
| Genomic Variant & GenBank ID: | 38,614,703 G>A on NT_022517 |
| mRNA Variant & GenBank ID: | 294 C>T on NM_000335 (transcript variant 2); 294 C>T on NM_198056 (transcript variant 1) |
| Protein Variant & GenBank ID: | 34 Arg>Cys on NP_000326 ; 34 Arg>Cys on NP_932173(the two sequences are for the two wild-type splice variants.) |
| dbSNP rs#: | rs6791924 |
| GoldenPath Position: | chr3:38649703 (hg18) |
| DNA Source Containing Homzygous Reference Allele(Coriell Lines): |
NA15362 (PA126721293) |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): |
NA15369 (PA126721271) |
| DNA Source Containing Homozygous Minor Allele(Coriell Lines): |
NA15380 (PA126721294) |
| Gene HGNC Name: | SCN5A |
|---|---|
| Variant Summary: | H558R was observed with a minor allelic frequency of 9.2% among Asians, 29% among blacks, 20.4% among whites and 23.1% among Hispanics [PMID: 15851227]. H558R was identified in both drug associated long QT patients (aLQTS) and controls. The frequency of this common nonsynonymous coding region polymorphism was no different between aLQTS patients and control subjects: 24% versus 19% [PMID: 11997281]. H558R has been reported to modulate a nearby mutation T512I that leads to an enhanced inactivation and conduction disease [PMID: 12569159]. When H558R was present with Q1077 (which is a splicing variant which makes up 35% of the transcript in human heart) , sodium current was profoundly reduced despite normal trafficking to the cell surface [PMID: 14500339]. |
| Key PubMed IDs: | 15851227, 11997281, 12569159, 14500339 |
| Genomic Variant & GenBank ID: | 38,585,424 T>C on NT_022517 |
| mRNA Variant & GenBank ID: | 1867 A>G on NM_000335 (transcript variant 2); 1867 A>G on NM_198056 (transcript variant 1) |
| Protein Variant & GenBank ID: | 558 His>Arg on NP_000326 ; 558 His>Arg on NP_932173 (the two sequences are for the two wild-type splice variants .) |
| dbSNP rs#: | rs1805124 |
| GoldenPath Position: | chr3:38620424 (hg18) |
| Key Drugs/Substrates: | |
| Key Phenotypes/Diseases: | H558R has been reported to modulate a nearby mutation T512I that leads to an enhanced inactivation and conduction disease [PMID: 12569159]. |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
NA15367 (PA126721270 ) |
| DNA Source Containing Heterozygous Reference Allele (Coriell Lines): |
NA15369 (PA126721271) |
| Phenotype Data Sets: | NA15216 (PA126721225) |
| Gene HGNC Name: | SCN5A |
|---|---|
| Variant Summary: | S1103Y was detected only among African Americans [PMID: 15851227, 12193783]. About 13.2% of African Americans carry the Y1103 allele. A small case-control study (123 patients and controls) reported a strong association between the variant allele and susceptibility to a range of arrhythmias in African Americans [PMID: 12193783]. The incidence of homozygotes was 3/133 SIDS subjects vs. 0/1056 controls; in vitro the variant produced an LQT3-like phenotype on exposure to external acid medium [PMID: 16453024]. |
| Key PubMed IDs: | 15851227, 12193783, 16453024 |
| Genomic Variant & GenBank ID: | 38,560,911 G>T on NT_022517 |
| mRNA Variant & GenBank ID: |
3499 C>A on NM_000335 (transcript variant 2); 3502 C>A on NM_198056 (transcript variant 1) |
| Protein Variant & GenBank ID: | 1102 Ser>Tyr on NP_000326 ; 1103 Ser>Tyr on NP_932173 (the two sequences are for the two wild-type splice variants.) |
| dbSNP rs#: | rs7626962 |
| GoldenPath Position: | chr3:38595911 (hg18) |
| Key Phenotypes/Diseases: | Susceptibility to arrhythmias in African Americans in a small association study [PMID: 12193783]; possible susceptibility to SIDS [PMID: 16453024]. |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
NA17149 (PA126721864) |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): |
NA17162 (PA126721782) |