ABCMdb

ABCC7 p.Pro140Ser

ClinVar:	c.418C>T , p.Pro140Ser ? , not provided c.419C>T , p.Pro140Leu ? , not provided
CF databases:	c.418C>T , p.Pro140Ser (CFTR1) ? , A novel mutation has been identified by DGGE and direct sequencing. The nucletoide change C->T, at position 550, leads to P140S in exon 4. c.419C>T , p.Pro140Leu (CFTR1) ? , This mutation was detected by DGGE and direct sequencing. P140L was found once (1/ 500 chromosomes) in a male CF patient of Greek origin; he presented with meconium at birth, PS and mild bronchitis.
Predicted by SNAP2:	A: N (78%), C: N (72%), D: N (57%), E: D (53%), F: D (59%), G: N (66%), H: N (53%), I: D (53%), K: D (59%), L: N (61%), M: N (53%), N: N (66%), Q: N (53%), R: D (59%), S: N (87%), T: N (78%), V: N (66%), W: D (75%), Y: D (53%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: D, G: D, H: N, I: D, K: N, L: D, M: N, N: N, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D,

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Publications
[hide] Preconception and prenatal cystic fibrosis carrier... Genet Med. 2004 May-Jun;6(3):141-4. Monaghan KG, Bluhm D, Phillips M, Feldman GL
Preconception and prenatal cystic fibrosis carrier screening of African Americans reveals unanticipated frequencies for specific mutations.
Genet Med. 2004 May-Jun;6(3):141-4., [PMID:15354332]

Abstract [show]
PURPOSE: It is recommended that cystic fibrosis (CF) carrier screening be made available to African Americans who are either pregnant or planning a pregnancy. We analyzed the carrier and mutant allele frequencies for African Americans undergoing CF carrier screening in our laboratories. METHODS: Between December 2001 and September 2003, we performed carrier screening for 2189 African Americans, testing for at least the 25 recommended mutations. RESULTS: A total of 33 CF carriers were identified. The most common mutations detected were deltaF508, G622D, R117H/7T, and G551D. The G622D allele frequency among African Americans was 0.18%. We did not detect any 3120 + 1G --> A carriers, although 4 were expected (P < 0.05). CONCLUSIONS: When considering only the 25 recommended CF mutations, 1 in 75 African Americans screened in our laboratories were carriers (within the expected range, given a 69% mutation detection rate). The addition of 2 mutations, G622D and Q98R (incidentally identified while screening for ACOG/ACMG mutations), increased the observed carrier frequency to 1 in 66, which is not significantly different from the known African American carrier frequency of 1 in 65. The frequencies of several specific mutations detected were unanticipated, as was the absence of 3120 + 1G --> A carriers. Further studies on African American patients with classic CF are needed to examine the incidence of CF mutations that are not part of the current panel, such as G622D.

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No. Sentence Comment
46 F693L (TTG) and P140S (C3T) are variants of unknown clinical significance. Login to comment
51 R117H has been previously reported at an increased frequency among individuals undergoing carrier screening compared to those with a diagnosis of cystic fibrosis.8 An unexpected result was the lack of 3120ϩ1G3A carriers, although 4 were expected given that this mutation accounts for Ϸ12% of the CF muta- Table 1 Summary of carrier screening results using various methods employed between December 2001 and September 2003 OLA v2.0, heteroduplex analysis (exons 4 and 13) and RFLP analysis (3120ϩ1G3A) OLA v3.0 INNO-LiPA Total screened 818 1274 97 No. of carriers identified 16 14 3 Observed carrier frequency 1/51 1/81 Mutations identified ⌬F508 (6), G622D (3), R117H/7T (3), I148T (3199del6 negative), Q98R, 1898ϩ1G3A, and G551Da ⌬F508 (14), R117H/7T, R553X, and G551D a In addition, 2 persons were positive for F693L (TTG) and 1 was positive for P140S (C3T at 550); both are variants of unknown clinical significance. Login to comment
57 Two mutations, G622D and Q98R, and two variants of unknown clinical significance, F693L (TTG) and P140S (C3T), which are not part of the recommended CF screening panel, were incidentally detected while using heteroduplex analysis to screen for ACOG/ACMG recommended mutations (Table 2). Login to comment
65 P140S (C3T) has been reported in a patient with disseminated bronchiectasis, although it is not known if this mutation is associated with classic CF.9 Q98R has been reported previously as a CF mutation,12 although we are not aware of any reports of this mutation in African Americans. Login to comment