Submissions for variant NM_000350.3(ABCA4):c.3586A>T (p.Thr1196Ser)

gnomAD frequency: 0.00004  dbSNP: rs370967816

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000391783	SCV000359395	uncertain significance	Retinitis Pigmentosa, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000305309	SCV000359396	uncertain significance	Cone-Rod Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000360005	SCV000359397	uncertain significance	Macular degeneration	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000260569	SCV000359398	uncertain significance	Stargardt Disease, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001096422	SCV001252630	uncertain significance	ABCA4-Related Disorders	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV002520513	SCV003448968	uncertain significance	not provided	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1196 of the ABCA4 protein (p.Thr1196Ser). This variant is present in population databases (rs370967816, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with ABCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 298249). 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 with a negative predictive value of 95%. 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.
Ambry Genetics	RCV003278751	SCV003961171	uncertain significance	Inborn genetic diseases	2023-05-26	criteria provided, single submitter	clinical testing	The c.3586A>T (p.T1196S) alteration is located in exon 24 (coding exon 24) of the ABCA4 gene. This alteration results from a A to T substitution at nucleotide position 3586, causing the threonine (T) at amino acid position 1196 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.