ClinVar Miner

Submissions for variant NM_172244.3(SGCD):c.160A>G (p.Ile54Val) (rs200671745)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725987 SCV000236384 uncertain significance not provided 2017-06-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SGCD gene. The I54V variant has not been published as pathogenic or been reported as benign to our knowledge. The I54V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species and in silico analysis suggests that this variant is probably damaging to the protein structure/function. However, he I54V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725987 SCV000341046 uncertain significance not provided 2018-08-10 criteria provided, single submitter clinical testing
Invitae RCV000545954 SCV000638168 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2F 2019-07-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 54 of the SGCD protein (p.Ile54Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs200671745, ExAC 0.04%). This variant has not been reported in the literature in individuals with SGCD-related disease. ClinVar contains an entry for this variant (Variation ID: 202087). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000183901 SCV000280485 uncertain significance not specified 2014-03-27 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Ile54Val (c.160 A>G) in the SGCD gene (NM_000337.5) Given the lack of case data we consider this variant a variant of uncertain significance. The variant is novel. In silico analysis with PolyPhen-2 predicts the variant to be benign and analysis with SIFT predicts it to be tolerated. However, GeneDx notes in their report that in silico analysis predicts it to be probably damaging (they do not note which program they used). The isoleucine at codon 54 is highly though not completely conserved across species, as are neighboring amino acids. In total the variant has been seen in 1 of 7389 individuals from publicly available population datasets. There is no variation at codon 54 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6300 Caucasian and African American individuals (as of May 29th, 2014). The variant was observed in 1 of 1089 individuals in the 1000 genomes phase 1 data (as of June 2nd, 2014). This individual was one of the 61 African American subjects. Of note this is low coverage sequencing data which may have false positives. The variant is listed in dbSNP (rs200671745) pointing to the 1000 genomes data (as of June 2nd, 2014).

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