ClinVar Miner

Submissions for variant NM_000337.5(SGCD):c.755C>T (p.Thr252Met) (rs199520526)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726990 SCV000236387 uncertain significance not provided 2017-04-03 criteria provided, single submitter clinical testing p.Thr252Met (ACG>ATG): c.755 C>T in exon 9 of the SGCD gene (NM_000337.5). A variant of unknown significance has been identified in the SGCD gene. The T252M variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T252M variant was not observed with any significant frequency in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes project, indicating it is not a common benign variant in these populations. The T252M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. One missense mutation in a nearby residue (E262K) has been reported in association with cardiomyopathy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726990 SCV000704737 uncertain significance not provided 2017-01-04 criteria provided, single submitter clinical testing
Invitae RCV000796070 SCV000935564 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2F 2019-11-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 252 of the SGCD protein (p.Thr252Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs199520526, ExAC 0.1%). This variant has not been reported in the literature in individuals with SGCD-related conditions. ClinVar contains an entry for this variant (Variation ID: 202089). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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