Submissions for variant NM_000037.4(ANK1):c.4156T>C (p.Tyr1386His)

gnomAD frequency: 0.00041  dbSNP: rs201439151

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000359380	SCV000473836	uncertain significance	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, 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755816	SCV000883400	uncertain significance	not provided	2017-10-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001162700	SCV001324662	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.
Ambry Genetics	RCV002523681	SCV003723122	uncertain significance	Inborn genetic diseases	2021-07-06	criteria provided, single submitter	clinical testing	The c.4156T>C (p.Y1386H) alteration is located in exon 34 (coding exon 34) of the ANK1 gene. This alteration results from a T to C substitution at nucleotide position 4156, causing the tyrosine (Y) at amino acid position 1386 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000359380	SCV003818556	uncertain significance	Hereditary spherocytosis type 1	2022-03-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003950288	SCV004760364	likely benign	ANK1-related condition	2021-08-04	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).