Submissions for variant NM_152443.3(RDH12):c.580dup (p.Tyr194fs)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001388911	SCV001590064	pathogenic	Leber congenital amaurosis 13	2022-02-04	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1075351). This variant has not been reported in the literature in individuals affected with RDH12-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr194Leufs*20) in the RDH12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RDH12 are known to be pathogenic (PMID: 17964524, 22065924). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003155408	SCV003844734	likely pathogenic	Leber congenital amaurosis	2023-02-14	criteria provided, single submitter	clinical testing	Variant summary: RDH12 c.580dupT (p.Tyr194LeufsX20) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been cited as pathogenic and disease-associated in ClinVar and HGMD. The variant was absent in 251396 control chromosomes. To our knowledge, no occurrence of c.580dupT in individuals affected with Leber Congenital Amaurosis and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV001388911	SCV004208615	likely pathogenic	Leber congenital amaurosis 13	2022-09-06	criteria provided, single submitter	clinical testing

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