ClinVar Miner

Submissions for variant NM_001283009.2(RTEL1):c.1205T>C (p.Val402Ala)

gnomAD frequency: 0.00046  dbSNP: rs137956338
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001246482 SCV001419840 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 402 of the RTEL1 protein (p.Val402Ala). This variant is present in population databases (rs137956338, gnomAD 0.1%). This missense change has been observed in individual(s) with myelodysplastic syndrome (PMID: 29344583). ClinVar contains an entry for this variant (Variation ID: 970832). 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 alanine 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.
Sema4, Sema4 RCV002256722 SCV002535281 uncertain significance Dyskeratosis congenita 2021-12-07 criteria provided, single submitter curation
GeneDx RCV002285465 SCV002575441 uncertain significance not provided 2022-09-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in an individual with hypocellular myelodysplastic syndrome and shortened telomeres, reported as p.Val402Ala using alternate nomenclature (Marsh et al., 2018); This variant is associated with the following publications: (PMID: 29344583)
Fulgent Genetics, Fulgent Genetics RCV001246482 SCV002780530 uncertain significance Dyskeratosis congenita, autosomal recessive 5; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 2022-02-05 criteria provided, single submitter clinical testing

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