Submissions for variant NM_000053.4(ATP7B):c.3305T>C (p.Ile1102Thr) (rs560952220)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Integrated Genetics/Laboratory Corporation of America	RCV000495835	SCV000694443	pathogenic	Wilson disease	2017-06-26	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.3305T>C (p.Ile1102Thr) variant located in the ATP loop (Luoma_2010) involves the alteration of a conserved nucleotide that 4/4 in silico tools predict a damaging outcome for this variant. A functional study, Luoma_2010, does indicate the variant inhibits normal ATP7B protein function. This variant was found in 1/120752 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). Multiple publications cite the variant in affected homozygote and compound heterozygote individuals. In addition, multiple reputable databases cite the variant as "pathogenic." Taken together, this variant is classified as pathogenic.
Foundation for Research in Genetics and Endocrinology,Institute of Human Genetics	RCV000495835	SCV000583503	likely pathogenic	Wilson disease		no assertion criteria provided	clinical testing	The observed mutation is reported in 1000 genomes and ExAC databases. Its dbSNP reference number is rs560952220. The in silico prediction of the observed mutation is disease-causing by Mutationtaster2 and probably damaging by PolyPhen2 and SIFT. The proband, born of a non consanguinous union was clinically diagnosed to be affected with Wilson's disease. Upon investigation it was found that the proband had c.3305T>C (p.I1102T) mutation in exon 15 of ATP7B gene. His parents were further investigated for the same mutation and were found to be heterozyous for the same by Sanger sequencing. Also during subsequent pregnancy the fetus was found to be heterozygous for the same mutation.