PhenoModifier-Variant Detail

Variant "CACNB2:c.1604C>T(p.Ser535Leu)"

Search result: 1 record

Variant information

Gene:

CACNB2

Variant:

CACNB2:c.1604C>T(p.Ser535Leu)

Genomic location:

chr10:18828274(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_201596.2:c.1604C>T(p.Ser535Leu)
protein_coding	NM_201597.2:c.1532C>T(p.Ser511Leu)
protein_coding	NM_201571.3:c.1520C>T(p.Ser507Leu)
protein_coding	NM_201593.2:c.1490C>T(p.Ser497Leu)
protein_coding	NM_201570.2:c.1460C>T(p.Ser487Leu)
protein_coding	NM_201572.3:c.1448C>T(p.Ser483Leu)
protein_coding	NM_201590.2:c.1442C>T(p.Ser481Leu)
protein_coding	NM_000724.3:c.1439C>T(p.Ser480Leu)
protein_coding	NM_001167945.1:c.1406C>T(p.Ser469Leu)
protein_coding	NM_001330060.1:c.1325C>T(p.Ser442Leu)
show all

dbSNP ID:

rs121917812

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Expressivity(1)

Modifier effect:

Altered severity(1)

Detail：

Target disease:

Hypertrophic Cardiomyopathy (DOID_11984)

Effect type:

Expressivity

Modifier effect:

Altered severity

Evidence:

Pedigree analysis

Effect:

CACNB2 is a possible genetic modifier of MYBPC3-associated familial HCM

Reference:

PMID28614222

Title:

Next-generation sequencing identifies pathogenic and modifier mutations in a consanguineous Chinese family with hypertrophic cardiomyopathy.

Species studied:

Human

Abstract:

Hypertrophic cardiomyopathy (HCM) is a highly heterogeneous disease displaying considerable interfamilial and intrafamilial phenotypic variation, including disease severity, age of onset, and disease progression. This poorly understood variance raises the possibility of genetic modifier effects, particularly in MYBPC3-associated HCM.In a large consanguineous Chinese HCM family, we identified 8 members harboring the MYBPC3 c.3624delC (p.Lys1209Serfs) disease-causing mutation, but with very disparate phenotypes. Genotyping ruled out the modifying effect of previously described variants in renin-angiotensin-aldosterone system. Afterwards, we screened for modifying variants in all known causing genes and closely related genes for cardiomyopathy and channelopathy by performing targeted next-generation sequencing. For first time, we showed that a c.1598C>T (p.Ser533Leu) mutation in voltage-dependent l-type calcium channel subunit beta-2 (CACNB2) was present in all severely affected HCM patients, but not in those moderately affected or genotype-positive phenotype-negative patients. This CACNB2 p.Ser533Leu mutation is extremely conserved in evolution, and was not found in 550 healthy controls.Our results suggest that CACNB2 is a possible candidate genetic modifier of MYBPC3-associated familial HCM, but more genetic evidence and functional experiments are needed to confirm.