Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000407838 | SCV000417601 | uncertain significance | Asphyxiating thoracic dystrophy 4 | 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. |
Illumina Laboratory Services, |
RCV000297705 | SCV000417602 | uncertain significance | Nephronophthisis 12 | 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. |
Invitae | RCV000861564 | SCV001001926 | benign | Jeune thoracic dystrophy; Nephronophthisis | 2023-12-09 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001812869 | SCV002048271 | uncertain significance | not provided | 2020-10-26 | criteria provided, single submitter | clinical testing | The TTC21B c.3914A>G, p.Asp1305Gly variant (rs147540469), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 331819). This variant is found in the general population with an allele frequency in Ashkenazi populations of 0.74% (77/10,360 alleles; including one homozygote) in the Genome Aggregation Database. The aspartic acid at codon 1305 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.562). Thus, based on the available information, the clinical significance of this variant is uncertain. |
Genetic Services Laboratory, |
RCV003151031 | SCV003839187 | uncertain significance | not specified | 2022-05-06 | no assertion criteria provided | clinical testing | DNA sequence analysis of the TTC21B gene demonstrated a sequence change, c.3914A>G, in exon 29 that results in an amino acid change, p.Asp1305Gly. This sequence change has been described in the gnomAD database with a frequency of 0.74% in the Ashkenazi Jewish subpopulation and includes one homozygous individual (dbSNP rs147540469). The p.Asp1305Gly change affects a moderately conserved amino acid residue located in a domain of the TTC21B protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asp1305Gly substitution. This sequence change does not appear to have been previously described in individuals with TTC21B-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Asp1305Gly change remains unknown at this time. |