Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000920257 | SCV001065619 | likely benign | not provided | 2024-10-28 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001112581 | SCV001270252 | uncertain significance | Autosomal recessive congenital ichthyosis 1 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002265909 | SCV002547990 | likely benign | not specified | 2022-05-31 | criteria provided, single submitter | clinical testing | Variant summary: TGM1 c.550C>T (p.Pro184Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00072 in 251354 control chromosomes, predominantly at a frequency of 0.0054 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in TGM1 causing Lamellar Ichthyosis phenotype (0.0021), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.550C>T has been reported in the literature in at-least one individual affected with congenital ichthyosiform erythroderma (CIE) (example, Numata_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Lamellar Ichthyosis. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Numata_2016). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=2; VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
| Gene |
RCV000920257 | SCV003845583 | uncertain significance | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | Observed with another TGM1 variant in a patient with ARCI in the published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Numata et al., 2015); Published functional studies suggest a damaging effect: formation of perinuclear aggregates and decreased localization to membranes (Numata et al., 2016); 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: 34426522, 33138774, 26990434, 25766764) |
| Natera, |
RCV001112581 | SCV002091234 | benign | Autosomal recessive congenital ichthyosis 1 | 2019-11-13 | no assertion criteria provided | clinical testing |