Submissions for variant NM_001283009.2(RTEL1):c.251G>C (p.Arg84Pro)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002963107	SCV003288673	uncertain significance	Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	2022-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 84 of the RTEL1 protein (p.Arg84Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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	RCV002963108	SCV003613206	uncertain significance	Inborn genetic diseases	2022-02-24	criteria provided, single submitter	clinical testing	The c.251G>C (p.R84P) alteration is located in exon 3 (coding exon 2) of the RTEL1 gene. This alteration results from a G to C substitution at nucleotide position 251, causing the arginine (R) at amino acid position 84 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV004794600	SCV005415272	uncertain significance	not provided	2024-05-20	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004736235	SCV005365421	uncertain significance	RTEL1-related disorder	2024-03-19	no assertion criteria provided	clinical testing	The RTEL1 c.251G>C variant is predicted to result in the amino acid substitution p.Arg84Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.036% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.