ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1829T>C (p.Leu610Pro)

gnomAD frequency: 0.00001  dbSNP: rs755196345
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176327 SCV001340265 uncertain significance Cardiomyopathy 2023-06-01 criteria provided, single submitter clinical testing This missense variant replaces leucine with proline at codon 610 of the DSG2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy and muscle weakness (PMID: 30165862). This variant has been identified in 6/280442 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001760126 SCV001990593 uncertain significance not provided 2019-04-30 criteria provided, single submitter clinical testing Reported in one Chinese individual with a clinical history of dilated cardiomyopathy (DCM) and muscle weakness (Lu et al., 2018); however, no segregation studies were described; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30165862)
Invitae RCV003517305 SCV004369838 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-01-14 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 918632). This missense change has been observed in individual(s) with clinical features of DSG2-related conditions (PMID: 30165862). This variant is present in population databases (rs755196345, gnomAD 0.03%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 610 of the DSG2 protein (p.Leu610Pro).

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