Submissions for variant NM_001148.6(ANK2):c.8927C>G (p.Ser2976Cys)

gnomAD frequency: 0.00002  dbSNP: rs371343942

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000618854	SCV000738134	likely benign	Cardiovascular phenotype	2023-04-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001051685	SCV001215853	uncertain significance	Long QT syndrome	2024-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2976 of the ANK2 protein (p.Ser2976Cys). This variant is present in population databases (rs371343942, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25351510). ClinVar contains an entry for this variant (Variation ID: 519493). 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.
GeneDx	RCV001571397	SCV001795865	uncertain significance	not provided	2024-04-24	criteria provided, single submitter	clinical testing	Reported in one individual with hypertrophic cardiomyopathy and one individual with unexplained sudden cardiac death in published literature (PMID: 25351510, 27332903); In silico analysis indicates that this missense variant does not alter protein structure/function; Located in exon 38, which is reported as being expressed in a brain-specific transcript (PMID: 1830053, 18790697, 26109584); This variant is associated with the following publications: (PMID: 27332903, 29057844, 1830053, 18790697, 26109584, 25351510)
Fulgent Genetics, Fulgent Genetics	RCV002483724	SCV002775746	uncertain significance	Cardiac arrhythmia, ankyrin-B-related	2021-10-05	criteria provided, single submitter	clinical testing
KardioGenetik, Herz- und Diabeteszentrum NRW	RCV002483724	SCV004363567	uncertain significance	Cardiac arrhythmia, ankyrin-B-related	2024-01-29	criteria provided, single submitter	clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252391	SCV001428146	likely benign	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing