ABCMdb

ABCA4 p.Tyr954Ser

ClinVar:	c.2860T>G , p.Tyr954Asp ? , not provided
Predicted by SNAP2:	A: D (71%), C: D (59%), D: D (80%), E: D (63%), F: N (53%), G: D (75%), H: D (53%), I: N (53%), K: D (66%), L: D (59%), M: D (59%), N: D (71%), P: D (75%), Q: D (63%), R: D (63%), S: D (66%), T: D (63%), V: D (53%), W: D (53%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D,

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Publications
[hide] Comparison of high-resolution melting analysis wit... Invest Ophthalmol Vis Sci. 2010 May;51(5):2615-9. Epub 2009 Dec 3. Aguirre-Lamban J, Riveiro-Alvarez R, Garcia-Hoyos M, Cantalapiedra D, Avila-Fernandez A, Villaverde-Montero C, Trujillo-Tiebas MJ, Ramos C, Ayuso C
Comparison of high-resolution melting analysis with denaturing high-performance liquid chromatography for mutation scanning in the ABCA4 gene.
Invest Ophthalmol Vis Sci. 2010 May;51(5):2615-9. Epub 2009 Dec 3., [PMID:19959634]

Abstract [show]
PURPOSE: Mutations in the ABCA4 gene have been associated with autosomal recessive Stargardt disease (STGD), a few cases of autosomal recessive cone-rod dystrophy (arCRD), and autosomal recessive retinitis pigmentosa (arRP). The purpose of this study was to compare high-resolution melting (HRM) analysis with denaturing high-performance liquid chromatography (dHPLC), to evaluate the efficiency of the different screening methodologies. METHODS: Thirty-eight STGD, 15 arCRD, and 5 arRP unrelated Spanish patients who had been analyzed with the ABCR microarray were evaluated. The results were confirmed by direct sequencing. In patients with either no or only one mutant allele, ABCA4 was further analyzed by HRM and dHPLC. Haplotype analysis was also performed. RESULTS: In a previous microarray analysis, 37 ABCA4 variants (37/116; 31.9%) were found. dHPLC and HRM scanning identified 18 different genotypes in 20 samples. Of the samples studied, 19/20 were identified correctly by HRM and 16/20 by dHPLC. One homozygous mutation was not detected by dHPLC; however, the p.Cys2137Tyr homozygote was distinguished from the wild-type by HRM technique. In the same way, one novel change in exon 5 (p.Arg187His) was found only by means of the HRM technique. In addition, dHPLC identified the mutation p.Trp1724Cys in one sample; however, HRM detected the mutation in two samples. CONCLUSIONS: ABCA4 should be analyzed by an optimal screening technique, to perform further characterization of pathologic alleles. The results seemed to show that HRM had better sensitivity and specificity than did dHPLC, with the advantage that some homozygous sequence alterations were identifiable.

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No. Sentence Comment
64 Except p.Arg187His and p.Tyr954Ser variants, the rest of changes were previously reported as disease-associated allele.14 The p.Arg187His and p.Tyr954Ser variants were not found in 100 ethnically matched control chromosomes. Login to comment
81 The p.Tyr954Ser variant had not been reported and was not found in 100 ethnically matched control chromosomes. Login to comment
87 Mutations Analyzed Family Exon Genotype Mutation Detected by dHPLC Mutation Detected by HRM Nucleotide Change Amino Acid Change ARDM-167 5 c.560G>A p.Arg187His No Yes ARDM-257 5 c.560G>A p.Arg187His No Yes ARDM-164 6 c.700CϾT p.Gln234X Yes Yes ARDM-135 8 c.1029_1030insT p.Asn344fsX Yes No ARDM-240 15 c.2285CϾA p.Ala762Glu Yes Yes ARDM-248 19 c.2861A>C p.Tyr954Ser Yes Yes ARDM-90 - IVS21-2AϾT - Yes Yes ARDM-40 27 c.3943CϾT p.Gln1315X Yes Yes ARDM-158 30 c.4537delC p.Gln1513fsX1525 Yes Yes ARDM-38 33 c.4739delT p.Leu1580fs Yes Yes ARDM-163 36 c.5172GϾT p.Trp1724Cys Not Yes ARDM-197 36 c.5172GϾT p.Trp1724Cys Yes Yes ARDM-181 - IVS38ϩ5GϾA - Yes Yes ARDM-125 40 - p.KNLFA1876dup Yes Yes ARDM-183 43 c.5929GϾA(False-) p.Gly1977Ser(False-) Yes Yes ARDM-146 44 c.6140TϾA p.lle2047Asn Yes Yes ARDM-174 - IVS44ϩ2TϾA - Yes Yes ARDM-247 47 c.6410GϾA p.Cys2137Tyr* Yes Yes ARDM-84 47 c.6410GϾA p.Cys2137Tyr† No Yes ARDM-225 48 c.6559CϾT p.Gln2187X Yes Yes Previously unreported mutations are shown in bold. Login to comment
109 The p.Tyr954Ser variant was not found in 100 ethnically matched control chromosomes, suggesting the presence of a disease-associated allele. Login to comment
61 Except p.Arg187His and p.Tyr954Ser variants, the rest of changes were previously reported as disease-associated allele.14 The p.Arg187His and p.Tyr954Ser variants were not found in 100 ethnically matched control chromosomes. Login to comment
78 The p.Tyr954Ser variant had not been reported and was not found in 100 ethnically matched control chromosomes. Login to comment
95 The p.Tyr954Ser variant was not found in 100 ethnically matched control chromosomes, suggesting the presence of a disease-associated allele. Login to comment