Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV002486481 | SCV002777212 | uncertain significance | Iodotyrosyl coupling defect; Autoimmune thyroid disease, susceptibility to, 3 | 2021-08-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001356073 | SCV004025275 | uncertain significance | not provided | 2023-02-09 | 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 |
Department of Pathology and Laboratory Medicine, |
RCV001356073 | SCV001551135 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The TG p.Arg2044Leu variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs573866267) and in control databases in 7 of 282480 chromosomes at a frequency of 0.00002478 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Other in 2 of 7210 chromosomes (freq: 0.000277), Latino in 2 of 35436 chromosomes (freq: 0.000056), African in 1 of 24908 chromosomes (freq: 0.00004) and European (non-Finnish) in 2 of 128938 chromosomes (freq: 0.000016), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) or South Asian populations. The p.Arg2044 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 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. |