Submissions for variant NM_007374.3(SIX6):c.385G>A (p.Glu129Lys)

gnomAD frequency: 0.00428  dbSNP: rs146737847

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514964	SCV000610513	uncertain significance	not provided	2017-04-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765177	SCV000896411	uncertain significance	Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome; Anophthalmia/microphthalmia-esophageal atresia syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000514964	SCV001020809	likely benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113381	SCV001271147	uncertain significance	Anophthalmia-microphthalmia syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000514964	SCV001885333	benign	not provided	2020-07-20	criteria provided, single submitter	clinical testing	Reported as a risk or hypomorphic allele in relation to primary open-angle glaucoma (Carnes et al., 2014; Iglesias et al., 2014; Shah et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24150847, 28499933, 28717659, 29165578, 24875647)
PreventionGenetics, part of Exact Sciences	RCV003915435	SCV004734286	likely benign	SIX6-related condition	2019-05-24	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).