Submissions for variant NM_005138.3(SCO2):c.535C>T (p.Arg179Cys)

gnomAD frequency: 0.00001  dbSNP: rs780314255

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197926	SCV000252237	uncertain significance	not provided	2024-04-14	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31589614)
Illumina Laboratory Services, Illumina	RCV001149868	SCV001310866	uncertain significance	Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001149869	SCV001310867	uncertain significance	Mitochondrial complex IV deficiency, nuclear type 1	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics	RCV001149868	SCV001523392	uncertain significance	Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1	2019-06-24	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV000197926	SCV002310633	uncertain significance	not provided	2022-03-05	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 179 of the SCO2 protein (p.Arg179Cys). This variant is present in population databases (rs780314255, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SCO2-related conditions. ClinVar contains an entry for this variant (Variation ID: 215130). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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	RCV002517259	SCV003555317	uncertain significance	Inborn genetic diseases	2022-07-28	criteria provided, single submitter	clinical testing	The c.535C>T (p.R179C) alteration is located in exon 2 (coding exon 1) of the SCO2 gene. This alteration results from a C to T substitution at nucleotide position 535, causing the arginine (R) at amino acid position 179 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.