Submissions for variant NM_000554.6(CRX):c.565G>C (p.Ala189Pro)

dbSNP: rs142111462

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001135986	SCV001295798	uncertain significance	Cone-rod dystrophy 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001135987	SCV001295799	uncertain significance	Retinitis pigmentosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001135988	SCV001295800	uncertain significance	Leber congenital amaurosis 7	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV001349508	SCV001543859	uncertain significance	Leber congenital amaurosis 7; Cone-rod dystrophy 2	2022-07-19	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 894659). This variant has not been reported in the literature in individuals affected with CRX-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 189 of the CRX protein (p.Ala189Pro).
MGZ Medical Genetics Center	RCV001135986	SCV002579032	uncertain significance	Cone-rod dystrophy 2	2022-04-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002556891	SCV003536505	uncertain significance	Inborn genetic diseases	2022-07-05	criteria provided, single submitter	clinical testing	The c.565G>C (p.A189P) alteration is located in exon 4 (coding exon 3) of the CRX gene. This alteration results from a G to C substitution at nucleotide position 565, causing the alanine (A) at amino acid position 189 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.