Submissions for variant NM_000037.4(ANK1):c.1153C>T (p.Arg385Cys)

gnomAD frequency: 0.00067  dbSNP: rs142626656

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000394	SCV001157182	uncertain significance	Hereditary spherocytosis type 1	2019-03-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001000394	SCV001323728	likely benign	Hereditary spherocytosis type 1	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001161824	SCV001323729	uncertain significance	Spherocytosis	2018-01-13	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	RCV001869418	SCV002138150	uncertain significance	not provided	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 385 of the ANK1 protein (p.Arg385Cys). This variant is present in population databases (rs142626656, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ANK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 810949). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV001869418	SCV002540948	uncertain significance	not provided	2022-12-28	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV003447570	SCV004175368	uncertain significance	Immunodeficiency 62	2022-09-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003928656	SCV004745371	likely benign	ANK1-related condition	2019-10-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).