Variant "RET:c.2071G>C(p.Gly691Arg)"
Search results: 2 records
Variant information
Gene:
RET 
Variant:
RET:c.2071G>C(p.Gly691Arg) 
Genomic location:
chr10:43610119(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_020975.4:c.2071G>C(p.Gly691Arg)
protein_coding NM_020630.4:c.2071G>C(p.Gly691Arg)
Alias:
RET:G691S 
dbSNP ID:
rs1799939  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
2 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered onset time(1) ,Risk factor(1)  
Details：
  • Target disease:
    Medullary thyroid carcinoma (Orphanet_1332)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Gene activity study 
    Effect:
    The RET-G691S non-synonymous polymorphism enhances in vitro the oncogenic activity of RET-S891A
    Alias in reference:
    RET:c.2071G>C(p.Gly691Arg)
    Reference:
    PMID25887804
    Title:
    The modifier role of RET-G691S polymorphism in hereditary medullary thyroid carcinoma: functional characterization and expression/penetrance studies.
    Species studied:
    Human
    Abstract:
    Hereditary medullary thyroid carcinoma (MTC) is caused by germ-line gain of function mutations in the RET proto-oncogene, and a phenotypic variability among carriers of the same mutation has been reported. We recently observed this phenomenon in a large familial MTC (FMTC) family carrying the RET-S891A mutation. Among genetic modifiers affecting RET-driven MTC, a role has been hypothesized for RET-G691S non-synonymous polymorphism, though the issue remains controversial. Aim of this study was to define the in vitro contribution of RET-G691S to the oncogenic potential of the RET-S891A, previously shown to harbour low transforming activity.
  • Target disease:
    Multiple Endocrine Neoplasia Type 2A (DOID_0050430)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    100% fisher's exact test, P<0.001 
    Effect:
    The G691S and S904S variants of RET have a modifier effect on the age at onset of MEN 2A
    Alias in reference:
    RET:G691S
    Reference:
    PMID12702567
    Title:
    Polymorphisms G691S/S904S of RET as genetic modifiers of MEN 2A.
    Species studied:
    Human
    Abstract:
    Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germ-line missense mutations in the RET proto-oncogene. Only a minor fraction of human disorders are simple monogenic diseases, and the identification of polymorphisms that increase susceptibility, including variations in pathological phenotypes, to human diseases is one of the key problems in medical genetics. To explore this idea, we analyzed the polymorphisms G691S (exon 11) and S904S (TCC-TCG, exon 15) of RET in 198 individuals corresponding to 35 unrelated Spanish MEN 2A families (104 patients with oncogenic MEN 2A mutation and 94 healthy relatives). We found strong cosegregation between both polymorphisms (100% Fisher's exact test, P < 0.001) using a control population containing 653 healthy individuals (362 females and 291 males). Interestingly, we found that the homozygous for these polymorphisms were, on average, 10 years younger at diagnosis compared with heterozygous and wild-type homozygous (P = 0.037). Taken together, all these findings could indicate that the G691S and S904S variants of RET have a modifier effect on the age at onset of MEN 2A. Moreover, compared with the control population, the homozygote status was significantly more prevalent in a series of 110 sporadic thyroid carcinoma (odds ratio = 2.36), suggesting that these polymorphisms may play a role as a low penetrance risk factor.