ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4130T>A (p.Ile1377Asn)

dbSNP: rs1215591946
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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 RCV001982322 SCV002211295 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2021-05-12 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DSP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with asparagine at codon 1377 of the DSP protein (p.Ile1377Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine.
Ambry Genetics RCV003167372 SCV003867564 uncertain significance Cardiovascular phenotype 2022-12-09 criteria provided, single submitter clinical testing The p.I1377N variant (also known as c.4130T>A), located in coding exon 23 of the DSP gene, results from a T to A substitution at nucleotide position 4130. The isoleucine at codon 1377 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.
Color Diagnostics, LLC DBA Color Health RCV003533065 SCV004363386 uncertain significance Cardiomyopathy 2024-03-07 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with asparagine at codon 1377 of the DSP 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251114 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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