Submissions for variant NM_001195518.2(MICU1):c.547C>T (p.Gln183Ter)

gnomAD frequency: 0.00001  dbSNP: rs777327250

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000254969	SCV000321891	pathogenic	not provided	2022-05-09	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29288388, 31130284, 28454995, 30264509, 33428302, 30919572, 29721912)
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000985189	SCV001438874	pathogenic	Proximal myopathy with extrapyramidal signs		criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814130	SCV001755137	pathogenic	Abnormality of the nervous system	2021-07-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000254969	SCV003441631	pathogenic	not provided	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln185*) in the MICU1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MICU1 are known to be pathogenic (PMID: 24336167). 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 premature translational stop signal has been observed in individual(s) with MICU1-related conditions (PMID: 29721912). ClinVar contains an entry for this variant (Variation ID: 265243). For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000985189	SCV004800993	uncertain significance	Proximal myopathy with extrapyramidal signs	2024-02-11	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000985189	SCV005076408	pathogenic	Proximal myopathy with extrapyramidal signs	2024-04-26	criteria provided, single submitter	clinical testing	Variant summary: CBARA1 c.553C>T (p.Gln185X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2e-05 in 204610 control chromosomes. c.553C>T has been reported in the literature in multiple individuals affected with MICU1 related conditions (Musa_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29721912). ClinVar contains an entry for this variant (Variation ID: 265243). Based on the evidence outlined above, the variant was classified as pathogenic.
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000985189	SCV001133207	likely pathogenic	Proximal myopathy with extrapyramidal signs	2019-09-26	no assertion criteria provided	clinical testing
OMIM	RCV000985189	SCV001335231	pathogenic	Proximal myopathy with extrapyramidal signs	2021-06-24	no assertion criteria provided	literature only