Submissions for variant NM_006277.3(ITSN2):c.443A>G (p.Asn148Ser)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003549093	SCV004266239	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 148 of the ITSN2 protein (p.Asn148Ser). This variant is present in population databases (rs150905984, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ITSN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2634580). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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	RCV004362868	SCV004890192	likely benign	not specified	2024-01-03	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.
PreventionGenetics, part of Exact Sciences	RCV003402667	SCV004118973	uncertain significance	ITSN2-related disorder	2024-02-14	no assertion criteria provided	clinical testing	The ITSN2 c.443A>G variant is predicted to result in the amino acid substitution p.Asn148Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.