ClinVar Miner

Submissions for variant NM_194279.4(ISCA2):c.297del (p.Phe99fs)

dbSNP: rs778755775
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008511 SCV001168283 likely pathogenic not provided 2018-12-28 criteria provided, single submitter clinical testing The c.297delT variant has been published in a two month old presenting with severe hypotonia and nystagmus who had decreased activities of complex II and IV in muscle tissue and who harbored a second variant in the ISCA2 gene on the opposite allele (in trans) (Toldo et al., 2018). The c.297delT variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.297delT variant causes a frameshift starting with codon Phenylalanine 99, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 18 of the new reading frame, denoted p.Phe99LeufsX18 (F99LfsX18). This variant is predicted to cause loss of normal protein function through protein truncation. In summary, we interpret c.297delT as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001008511 SCV004262558 uncertain significance not provided 2023-03-30 criteria provided, single submitter clinical testing 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 545531). This premature translational stop signal has been observed in individual(s) with clinical features consistent with multiple mitochondrial dysfunctions syndrome (PMID: 29359243). This variant is present in population databases (rs778755775, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Phe99Leufs*18) in the ISCA2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 56 amino acid(s) of the ISCA2 protein.
GeneReviews RCV000656511 SCV000747730 not provided Multiple mitochondrial dysfunctions syndrome 4 no assertion provided literature only
OMIM RCV000656511 SCV000778508 pathogenic Multiple mitochondrial dysfunctions syndrome 4 2018-06-15 no assertion criteria provided literature only

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