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NM_001283009.2(RTEL1):c.1344G>C (p.Lys448Asn) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 9, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001309490.4

Allele description [Variation Report for NM_001283009.2(RTEL1):c.1344G>C (p.Lys448Asn)]

NM_001283009.2(RTEL1):c.1344G>C (p.Lys448Asn)

Genes:
RTEL1-TNFRSF6B:RTEL1-TNFRSF6B readthrough (NMD candidate) [Gene - HGNC]
RTEL1:regulator of telomere elongation helicase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.33
Genomic location:
Preferred name:
NM_001283009.2(RTEL1):c.1344G>C (p.Lys448Asn)
HGVS:
  • NC_000020.11:g.63685868G>C
  • NG_033901.1:g.33059G>C
  • NM_001283009.2:c.1344G>CMANE SELECT
  • NM_001283010.1:c.675G>C
  • NM_016434.4:c.1344G>C
  • NM_032957.5:c.1416G>C
  • NP_001269938.1:p.Lys448Asn
  • NP_001269939.1:p.Lys225Asn
  • NP_057518.1:p.Lys448Asn
  • NP_116575.3:p.Lys472Asn
  • NP_116575.3:p.Lys472Asn
  • LRG_1149t1:c.1416G>C
  • LRG_1149t2:c.1344G>C
  • LRG_1149t3:c.1344G>C
  • LRG_1149:g.33059G>C
  • LRG_1149p1:p.Lys472Asn
  • LRG_1149p2:p.Lys448Asn
  • LRG_1149p3:p.Lys448Asn
  • NC_000020.10:g.62317221G>C
  • NM_032957.4:c.1416G>C
  • NR_037882.1:n.2171G>C
Protein change:
K225N
Links:
dbSNP: rs755129499
NCBI 1000 Genomes Browser:
rs755129499
Molecular consequence:
  • NM_001283009.2:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001283010.1:c.675G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016434.4:c.1344G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032957.5:c.1416G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_037882.1:n.2171G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Dyskeratosis congenita, autosomal recessive 5 (DKCB5)
Identifiers:
MONDO: MONDO:0014076; MedGen: C3554656; OMIM: 615190
Name:
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3
Synonyms:
PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 3
Identifiers:
MONDO: MONDO:0014613; MedGen: C4225346; Orphanet: 2032; OMIM: 616373

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001498990Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 9, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes.

Ghemlas I, Li H, Zlateska B, Klaassen R, Fernandez CV, Yanofsky RA, Wu J, Pastore Y, Silva M, Lipton JH, Brossard J, Michon B, Abish S, Steele M, Sinha R, Belletrutti M, Breakey VR, Jardine L, Goodyear L, Sung L, Dhanraj S, Reble E, et al.

J Med Genet. 2015 Sep;52(9):575-84. doi: 10.1136/jmedgenet-2015-103270. Epub 2015 Jul 1.

PubMed [citation]
PMID:
26136524

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001498990.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 448 of the RTEL1 protein (p.Lys448Asn). This variant is present in population databases (rs755129499, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of dyskeratosis congenita (PMID: 26136524). This variant is also known as c.1416G>C (p.Lys472Asn). ClinVar contains an entry for this variant (Variation ID: 550004). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024