Submissions for variant NM_000350.3(ABCA4):c.740A>C (p.Asn247Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003490859	SCV004241039	uncertain significance	not specified	2023-12-13	criteria provided, single submitter	clinical testing	Variant summary: ABCA4 c.740A>C (p.Asn247Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251460 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.740A>C has been reported in the literature in at least one individual affected with ABCA4-related retinopathy (e.g., Fujinami_2013, Cornelis_2017, Glinton_2022, Daich-Varela_2023). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23982839, 36178783, 28044389, 37331482). No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Dept Of Ophthalmology, Nagoya University	RCV003889306	SCV004706716	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research