Submissions for variant NM_080424.4(SP110):c.1020_1043dup (p.Cys342_Glu349dup)

dbSNP: rs769621341

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001280950	SCV001468304	uncertain significance	Hepatic veno-occlusive disease-immunodeficiency syndrome; Mycobacterium tuberculosis, susceptibility to	2021-11-22	criteria provided, single submitter	clinical testing	SP110 NM_004509.3 exon 9 p.Cys342_Glu349dup (c.1020_1043dup):This variant has not been reported in the literature but is present in 0.01% (15/129168) of Finnish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/2-231067299-T-TGATCTCGACTTTCGGGCACATTCA?dataset=gnomad_r2_1). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame duplication of 8 amino acids at position 342 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001365812	SCV001562095	uncertain significance	Hepatic veno-occlusive disease-immunodeficiency syndrome	2022-08-05	criteria provided, single submitter	clinical testing	This variant, c.1020_1043dup, results in the insertion of 8 amino acid(s) of the SP110 protein (p.Cys342_Glu349dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs769621341, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SP110-related conditions. ClinVar contains an entry for this variant (Variation ID: 992484). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.