Submissions for variant NM_001048166.1(STIL):c.892A>G (p.Asn298Asp)

gnomAD frequency: 0.00004  dbSNP: rs770213403

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000713539	SCV000334360	uncertain significance	not provided	2015-08-21	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000713539	SCV000844161	uncertain significance	not provided	2017-12-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763949	SCV000894896	uncertain significance	Microcephaly 7, primary, autosomal recessive	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000713539	SCV001787269	uncertain significance	not provided	2021-01-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000713539	SCV002151871	uncertain significance	not provided	2021-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine with aspartic acid at codon 298 of the STIL protein (p.Asn298Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs770213403, ExAC 0.1%). This variant has not been reported in the literature in individuals affected with STIL-related conditions. ClinVar contains an entry for this variant (Variation ID: 282750). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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	RCV004021115	SCV004960040	likely benign	Inborn genetic diseases	2022-04-14	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	RCV003977747	SCV004795612	likely benign	STIL-related disorder	2023-01-28	no assertion criteria provided	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).