ClinVar Miner

Submissions for variant NM_002582.4(PARN):c.448C>T (p.Arg150Cys)

gnomAD frequency: 0.00004  dbSNP: rs777558836
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital 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.

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