Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000756307 | SCV000884076 | uncertain significance | not provided | 2018-05-03 | criteria provided, single submitter | clinical testing | The LIFR: p.Asp1074Gly variant (rs147058538) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.02 percent (identified on 50 out of 277,068 chromosomes). This is a missense variant in a moderately conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor site weakening nearby interaction with exonic splicing enhancers. The aspartic acid at position 1074 is highly conserved up to frog considering 12 species and computational analyses of the effects of the p.Asp1074Gly variant on protein structure and function provide conflicting results (SIFT: tolerated, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Asp1074Gly variant with certainty. |
Illumina Laboratory Services, |
RCV001151740 | SCV001312905 | uncertain significance | Stuve-Wiedemann 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. |
Invitae | RCV000756307 | SCV003256143 | uncertain significance | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1074 of the LIFR protein (p.Asp1074Gly). This variant is present in population databases (rs147058538, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LIFR-related conditions. ClinVar contains an entry for this variant (Variation ID: 618197). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C35"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Ambry Genetics | RCV002533786 | SCV003692192 | uncertain significance | Inborn genetic diseases | 2021-11-15 | criteria provided, single submitter | clinical testing | The c.3221A>G (p.D1074G) alteration is located in exon 20 (coding exon 19) of the LIFR gene. This alteration results from a A to G substitution at nucleotide position 3221, causing the aspartic acid (D) at amino acid position 1074 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001151740 | SCV002084250 | uncertain significance | Stuve-Wiedemann syndrome | 2020-02-11 | no assertion criteria provided | clinical testing |