ClinVar Miner

Submissions for variant NM_014000.3(VCL):c.2528C>T (p.Pro843Leu)

gnomAD frequency: 0.00001  dbSNP: rs764302249
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483232 SCV000574007 uncertain significance not provided 2017-03-15 criteria provided, single submitter clinical testing The P843L variant has not been published aspathogenic or been reported as benign to our knowledge. It is not observed at a significant frequency in largepopulation cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P843Lvariant is a semi-conservative amino acid substitution, which may impact secondary protein structure as theseresidues differ in some properties. Moreover, this substitution occurs at a position that is conserved across species,and two of three in silico models predict this variant is probably damaging to the protein structure/function.Nonetheless, this variant lacks observation in a significant number of affected individuals, segregation data, andfunctional evidence, all of which would further clarify pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV001236366 SCV001409089 uncertain significance Dilated cardiomyopathy 1W 2023-07-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 424219). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with VCL-related conditions. This variant is present in population databases (rs764302249, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 843 of the VCL protein (p.Pro843Leu).
Fulgent Genetics, Fulgent Genetics RCV002506181 SCV002814543 uncertain significance Dilated cardiomyopathy 1W; Hypertrophic cardiomyopathy 15 2021-09-01 criteria provided, single submitter clinical testing

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