Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001080329 | SCV000373176 | uncertain significance | Cutis laxa, autosomal recessive, type 1B | 2018-01-13 | 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. |
Ce |
RCV000658599 | SCV000780377 | uncertain significance | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001080329 | SCV000818630 | benign | Cutis laxa, autosomal recessive, type 1B | 2023-12-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000658599 | SCV001982517 | uncertain significance | not provided | 2021-09-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26582918) |
Ambry Genetics | RCV002379175 | SCV002695153 | uncertain significance | Cardiovascular phenotype | 2021-06-29 | criteria provided, single submitter | clinical testing | The p.R326H variant (also known as c.977G>A), located in coding exon 9 of the EFEMP2 gene, results from a G to A substitution at nucleotide position 977. The arginine at codon 326 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Department of Pathology and Laboratory Medicine, |
RCV000658599 | SCV001549334 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The EFEMP2 p.(Arg326His) variant was not identified in the literature. The variant was found in dbSNP (ID: rs141868759) as "With Uncertain significance allele". ClinVar (the variant is classifed as a VUS, submitted by: Illumina Clinical Services Laboratory, Praxis fuer Humangenetik Tuebingen and Invitae. Associated conditions are Cutis laxa (recessive) and autosomal recessive cutis laxa type 1B.), Clinvitae (variant has been classified as a Variant of Uncertain Significance). Cosmic (FATHMM prediction Pathogenic (score 0.81)) and LOVD 3.0 (variant is listed with unknown effect), databases. The variant was identified in control databases in 86 of 281156 chromosomes at a frequency of 0.000306 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 76 of 10294 chromosomes (freq: 0.007383), Other in 2 of 7172 chromosomes (freq: 0.000279), European (non-Finnish) in 7 of 128034 chromosomes (freq: 0.000055) and Latino in 1 of 35340 chromosomes (freq: 0.000028); it was not observed in the African, East Asian, European (Finnish) and South Asian populations. The p.Arg326 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the R variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The p.(Arg326His) variant occurs in the last three bases of the exon. This position has been shown to be part of the splicing consensus sequence and variants involving this position sometimes affect splicing. However, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |