Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000284548 | SCV000477035 | uncertain significance | Oculocutaneous albinism type 3 | 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. |
Labcorp Genetics |
RCV001850933 | SCV002147168 | uncertain significance | not provided | 2022-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 70 of the TYRP1 protein (p.Ala70Thr). This variant is present in population databases (rs61752864, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 28976636, 31719542). ClinVar contains an entry for this variant (Variation ID: 364852). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TYRP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV002480252 | SCV002797733 | uncertain significance | Oculocutaneous albinism type 3; MELANESIAN BLOND HAIR | 2021-08-20 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323525 | SCV004028803 | uncertain significance | not specified | 2023-07-27 | criteria provided, single submitter | clinical testing | Variant summary: TYRP1 c.208G>A (p.Ala70Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 249952 control chromosomes. c.208G>A has been reported in the literature in individuals with clinical features of oculocutaneous albinism (examples: Campbell_2019, Marti_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Oculocutaneous albinism 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: 31719542, 28976636). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |