Submissions for variant NM_007374.3(SIX6):c.532_536del (p.Asn178fs)

dbSNP: rs786205142

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414384	SCV000491273	likely pathogenic	not provided	2017-04-18	criteria provided, single submitter	clinical testing	The c.532_536delAACCG variant in the SIX6 gene has been reported previously in the homozygous state in two siblings with micropthalmia (Aldahmesh et al., 2013). The c.532_536delAACCG variant causes a frameshift starting with codon Asparagine 178, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 142 of the new reading frame, with the last 69 amnio acids being replaced by 141 aberrant amino acids, denoted p.Asn178ProfsX142. This alteration may interfere with the proper formation and/or function of the SIX6 protein. The c.532_536delAACCG variant was not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server) The c.532_536delAACCG variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
CeGaT Center for Human Genetics Tuebingen	RCV000414384	SCV001501030	likely pathogenic	not provided	2021-06-01	criteria provided, single submitter	clinical testing
OMIM	RCV000169773	SCV000221335	pathogenic	Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome	2013-08-01	no assertion criteria provided	literature only