ClinVar Miner

Submissions for variant NM_003366.4(UQCRC2):c.361T>C (p.Tyr121His)

gnomAD frequency: 0.00014  dbSNP: rs778618710
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493198 SCV000583068 likely pathogenic not provided 2023-05-26 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Baylor Genetics RCV001331050 SCV001522967 uncertain significance Mitochondrial complex III deficiency nuclear type 5 2019-03-07 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV000493198 SCV002235874 uncertain significance not provided 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 121 of the UQCRC2 protein (p.Tyr121His). This variant is present in population databases (rs778618710, gnomAD 0.06%). This missense change has been observed in individual(s) with mitochondrial complex III deficiency (external communication). ClinVar contains an entry for this variant (Variation ID: 430295). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt UQCRC2 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.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV001331050 SCV002512426 uncertain significance Mitochondrial complex III deficiency nuclear type 5 2022-02-08 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 moderate
3billion RCV001331050 SCV003841946 uncertain significance Mitochondrial complex III deficiency nuclear type 5 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.008%). Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.63). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.

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