Submissions for variant NM_018834.6(MATR3):c.1879C>G (p.Gln627Glu)

gnomAD frequency: 0.00001  dbSNP: rs772231433

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000260341	SCV000453173	likely benign	Amyotrophic lateral sclerosis type 21	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000260341	SCV002109700	uncertain significance	Amyotrophic lateral sclerosis type 21	2024-10-28	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 627 of the MATR3 protein (p.Gln627Glu). This variant is present in population databases (rs772231433, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MATR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 351130). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MATR3 protein function with a negative predictive value of 80%. 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	RCV004021984	SCV004903388	uncertain significance	Inborn genetic diseases	2024-01-22	criteria provided, single submitter	clinical testing	The c.1879C>G (p.Q627E) alteration is located in exon 15 (coding exon 11) of the MATR3 gene. This alteration results from a C to G substitution at nucleotide position 1879, causing the glutamine (Q) at amino acid position 627 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.