Submissions for variant NM_004278.4(PIGL):c.258_259del (p.Glu86fs)

dbSNP: rs763616470

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000330257	SCV000400863	uncertain significance	Coloboma, Congenital Heart Disease, Ichthyosiform Dermatosis, Intellectual Disability, and Ear Anomalies (CHIME) Syndrome	2016-06-14	criteria provided, single submitter	clinical testing	The c.254_255delGA (p.Glu86AspfsTer3) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.00023 in the East Asian population of the Exome Aggregation Consortium, but this is based on two alleles so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, and ear anomalies syndrome.
Illumina Laboratory Services, Illumina	RCV000778489	SCV000914751	uncertain significance	CHIME syndrome	2017-04-27	criteria provided, single submitter	clinical testing	The PIGL c.254_255delGA (p.Glu86AspfsTer3) variant results in a frameshift and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.00023 in the East Asian population of the Exome Aggregation Consortium, but this is based on two alleles in a region of good sequencing coverage so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for coloboma, congenital heart disease, ichthyosiform dermatosis, intellectual disability, and ear anomalies syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.