Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000001642 | SCV000376743 | likely benign | Tyrosinemia type III | 2017-04-27 | 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV000386406 | SCV000376744 | likely benign | Hawkinsinuria | 2017-04-27 | 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Invitae | RCV000953322 | SCV001099887 | benign | Hawkinsinuria; Tyrosinemia type III | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000386406 | SCV001138848 | uncertain significance | Hawkinsinuria | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001091863 | SCV001248117 | likely benign | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | HPD: BS2 |
Gene |
RCV001091863 | SCV001850174 | likely benign | not provided | 2018-12-06 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 10942115, 25219469, 17560158) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488319 | SCV004241268 | likely benign | not specified | 2023-12-18 | criteria provided, single submitter | clinical testing | Variant summary: HPD c.1005C>G (p.Ile335Met) results in a 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 0.002 in 251474 control chromosomes, predominantly at a frequency of 0.0073 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 7-fold of the estimated maximal expected allele frequency for a pathogenic variant in HPD causing Tyrosinemia Type 3 phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.1005C>G has been reported in the literature in individuals affected with Tyrosinemia Type 3 without strong evidence for causality (Ganapathy_2019, Ruetschi_2000). These report(s) do not provide unequivocal conclusions about association of the variant with Tyrosinemia Type 3. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31069529, 10942115). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (Benign/Likely benign, n=4; VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
OMIM | RCV000001642 | SCV000021798 | pathogenic | Tyrosinemia type III | 2000-06-01 | no assertion criteria provided | literature only |