Submissions for variant NM_014000.3(VCL):c.818T>C (p.Ile273Thr)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001316014	SCV001506614	uncertain significance	Dilated cardiomyopathy 1W	2022-02-10	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. 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 1016938). This variant has not been reported in the literature in individuals affected with VCL-related conditions. This variant is present in population databases (rs762380935, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 273 of the VCL protein (p.Ile273Thr).
GeneDx	RCV002281182	SCV002569857	uncertain significance	not provided	2022-08-23	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics	RCV002431897	SCV002681194	uncertain significance	Cardiovascular phenotype	2021-05-27	criteria provided, single submitter	clinical testing	The p.I273T variant (also known as c.818T>C), located in coding exon 7 of the VCL gene, results from a T to C substitution at nucleotide position 818. The isoleucine at codon 273 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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