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

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Integrated Genetics/Laboratory Corporation of America	RCV000495835	SCV000694443	pathogenic	Wilson disease	2020-09-21	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.3305T>C (p.Ile1102Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 249578 control chromosomes (gnomAD). c.3305T>C has been reported in the literature in multiple individuals affected with Wilson Disease (example: Butler_2001, Kumar_2007, Dastsooz_2013). These data indicate that the variant is very likely to be associated with disease. In a yeast complementation functional assay, the variant was found to have intermediate to severe deficit (Luoma_2010). One other ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Centogene AG - the Rare Disease Company	RCV000495835	SCV001424370	pathogenic	Wilson disease		criteria provided, single submitter	clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's 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.
Counsyl	RCV000495835	SCV001132340	pathogenic	Wilson disease	2015-09-24	no assertion criteria provided	clinical testing

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