Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000723916 | SCV000202714 | uncertain significance | not provided | 2017-11-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000227560 | SCV000285814 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 387 of the FKTN protein (p.Gly387Arg). This variant is present in population databases (rs148975262, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FKTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 167070). 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. 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. |
Illumina Laboratory Services, |
RCV000339058 | SCV000476429 | uncertain significance | Dilated cardiomyopathy 1X | 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, |
RCV000406528 | SCV000476430 | uncertain significance | Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 | 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 |
RCV000723916 | SCV000566772 | uncertain significance | not provided | 2022-05-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#167070 ClinVar); This variant is associated with the following publications: (PMID: 30564623) |
Ambry Genetics | RCV000620716 | SCV000735845 | uncertain significance | Cardiovascular phenotype | 2022-12-06 | criteria provided, single submitter | clinical testing | The p.G387R variant (also known as c.1159G>A), located in coding exon 8 of the FKTN gene, results from a G to A substitution at nucleotide position 1159. The glycine at codon 387 is replaced by arginine, an amino acid with dissimilar 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. |
Athena Diagnostics Inc | RCV000723916 | SCV001143894 | uncertain significance | not provided | 2018-11-26 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000723916 | SCV001716029 | uncertain significance | not provided | 2020-10-13 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002498728 | SCV002812669 | uncertain significance | Dilated cardiomyopathy 1X; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4; Autosomal recessive limb-girdle muscular dystrophy type 2M; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1; Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4 | 2022-05-19 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509255 | SCV002819666 | uncertain significance | not specified | 2022-12-19 | criteria provided, single submitter | clinical testing | Variant summary: FKTN c.1159G>A (p.Gly387Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00043 in 250638 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in FKTN causing Cardiomyopathy (0.00043 vs 0.005), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1159G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (Internal data, MYBPC3, c.3627+1G>A), providing supporting evidence for a benign role. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Revvity Omics, |
RCV000723916 | SCV003832705 | uncertain significance | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000227560 | SCV002081969 | uncertain significance | Walker-Warburg congenital muscular dystrophy | 2020-04-03 | no assertion criteria provided | clinical testing |