Submissions for variant NM_000350.3(ABCA4):c.4765G>A (p.Val1589Met)

gnomAD frequency: 0.00001  dbSNP: rs767980304

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001073758	SCV001239318	uncertain significance	Retinal dystrophy	2017-11-30	criteria provided, single submitter	clinical testing
Invitae	RCV001359813	SCV001555698	uncertain significance	not provided	2022-06-20	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1589 of the ABCA4 protein (p.Val1589Met). This variant is present in population databases (rs767980304, gnomAD 0.005%). This missense change has been observed in individual(s) with ABCA4-associated conditions (PMID: 30670881). ClinVar contains an entry for this variant (Variation ID: 866045). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABCA4 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001359813	SCV001961121	uncertain significance	not provided	2021-09-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002505662	SCV002814928	uncertain significance	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2021-11-09	criteria provided, single submitter	clinical testing