Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000373402 | SCV000465086 | uncertain significance | Lethal acantholytic epidermolysis bullosa | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV001095250 | SCV000465088 | uncertain significance | Arrhythmogenic right ventricular dysplasia 8 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Laboratory Services, |
RCV000391545 | SCV000465089 | uncertain significance | Woolly hair-skin fragility syndrome | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Gene |
RCV000435354 | SCV000535503 | uncertain significance | not provided | 2016-12-29 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DSP gene. The S1629I variant has not been published in association with cardiomyopathy, however, it has been reported in one healthy control individual (Kapplinger et al., 2011). This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S1629I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is only conserved in mammals and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time. |
Invitae | RCV000547728 | SCV000641315 | benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000619025 | SCV000738200 | uncertain significance | Cardiovascular phenotype | 2017-10-17 | criteria provided, single submitter | clinical testing | The p.S1629I variant (also known as c.4886G>T), located in coding exon 23 of the DSP gene, results from a G to T substitution at nucleotide position 4886. The serine at codon 1629 is replaced by isoleucine, an amino acid with dissimilar properties. This alteration was detected in an ostensibly healthy control individual in one study; however, clinical details were limited (Kapplinger JD et al. J. Am. Coll. Cardiol., 2011 Jun;57:2317-27). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000777787 | SCV000913765 | likely benign | Cardiomyopathy | 2019-11-22 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000777787 | SCV000995748 | likely benign | Cardiomyopathy | 2019-01-22 | criteria provided, single submitter | clinical testing | |
Blueprint Genetics | RCV000157200 | SCV000206924 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2014-10-14 | no assertion criteria provided | clinical testing |