Submissions for variant NM_001195518.2(MICU1):c.88C>T (p.Arg30Trp)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002976051	SCV003287404	uncertain significance	not provided	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 30 of the MICU1 protein (p.Arg30Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MICU1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2074118). 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.
Ambry Genetics	RCV004065039	SCV004905559	uncertain significance	Inborn genetic diseases	2023-11-27	criteria provided, single submitter	clinical testing	The c.88C>T (p.R30W) alteration is located in exon 2 (coding exon 1) of the MICU1 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the arginine (R) at amino acid position 30 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM	RCV004555642	SCV005044761	uncertain significance	Proximal myopathy with extrapyramidal signs		criteria provided, single submitter	clinical testing	The missense variant c.367G>Ap.Gly123Arg in ALG12 gene has been reported in homozygous state in pateint affected with Congenital disorder of glycosylation, type Ig Nicotera et. al., 2021. The p.Gly123Arg variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance / Likely Pathogenic. The amino acid change p.Gly123Arg in ALG12 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Gly at position 123 is changed to a Arg changing protein sequence and it might alter its composition and physicochemical properties. For these reasons, this variant has been classified as Uncertain Significance VUS.