Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Genomic Medicine |
RCV001249632 | SCV001423596 | likely pathogenic | Dyskeratosis congenita, autosomal recessive 6 | 2017-05-31 | criteria provided, single submitter | clinical testing | [ACMG/AMP: PM1, PM2, PS3_Moderate, PP3] This alteration is located in a mutational hotspot and/or critical and well-established functional domain [PM1], is absent from or rarely observed in large-scale population databases [PM2], is supported by well-established in vitro or in vivo functional studies to have a damaging effect on protein function or splicing [PS3_Moderate], is predicted to be damaging by multiple functional prediction tools [PP3]. |
Invitae | RCV001879757 | SCV002294293 | uncertain significance | Dyskeratosis congenita, autosomal recessive 6; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 | 2022-05-21 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs777558836, gnomAD 0.008%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 973231). This variant has not been reported in the literature in individuals affected with PARN-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 150 of the PARN protein (p.Arg150Cys). |
Ambry Genetics | RCV002568697 | SCV003713196 | uncertain significance | Inborn genetic diseases | 2021-09-13 | criteria provided, single submitter | clinical testing | The c.448C>T (p.R150C) alteration is located in exon 7 (coding exon 7) of the PARN gene. This alteration results from a C to T substitution at nucleotide position 448, causing the arginine (R) at amino acid position 150 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |