ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.2622C>G (p.Ile874Met)

gnomAD frequency: 0.00004  dbSNP: rs751067479
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181303 SCV000233594 uncertain significance not provided 2023-05-24 criteria provided, single submitter clinical testing Identified in a patient with DCM in published literature (Pena-Pena et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32826072)
Labcorp Genetics (formerly Invitae), Labcorp RCV000535270 SCV000641297 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-12-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617477 SCV000737910 uncertain significance Cardiovascular phenotype 2024-03-20 criteria provided, single submitter clinical testing The p.I874M variant (also known as c.2622C>G), located in coding exon 18 of the DSP gene, results from a C to G substitution at nucleotide position 2622. The isoleucine at codon 874 is replaced by methionine, an amino acid with highly similar properties. This variant has been reported in association with dilated cardiomyopathy (DCM) (Peña-Peña ML et al. Med Clin (Barc), 2021 May;156:485-495). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769222 SCV000900598 uncertain significance Cardiomyopathy 2016-12-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000769222 SCV000904672 uncertain significance Cardiomyopathy 2024-03-06 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 874 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 12/282506 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.
Fulgent Genetics, Fulgent Genetics RCV002485190 SCV002800820 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis 2021-10-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996648 SCV004819682 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-09-23 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 874 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 12/282506 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.

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