Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000352840 | SCV000451500 | uncertain significance | Hypophosphatemic rickets, autosomal recessive, 1 | 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. |
| Fulgent Genetics, |
RCV000352840 | SCV002815894 | uncertain significance | Hypophosphatemic rickets, autosomal recessive, 1 | 2022-04-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002520282 | SCV003261830 | uncertain significance | not provided | 2022-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 143 of the DMP1 protein (p.Thr143Ile). This variant is present in population databases (rs370153862, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with DMP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 349973). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Ambry Genetics | RCV002520283 | SCV003689367 | uncertain significance | Inborn genetic diseases | 2022-11-10 | criteria provided, single submitter | clinical testing | The c.428C>T (p.T143I) alteration is located in exon 6 (coding exon 5) of the DMP1 gene. This alteration results from a C to T substitution at nucleotide position 428, causing the threonine (T) at amino acid position 143 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004701441 | SCV005204548 | uncertain significance | not specified | 2024-06-20 | criteria provided, single submitter | clinical testing | Variant summary: DMP1 c.428C>T (p.Thr143Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00027 in 251162 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in DMP1 causing Hypophosphatemic Rickets, Autosomal Recessive, 1, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.428C>T in individuals affected with Hypophosphatemic Rickets, Autosomal Recessive, 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 349973). Based on the evidence outlined above, the variant was classified as uncertain significance. |