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NM_000321.3(RB1):c.1997G>T (p.Cys666Phe) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 17, 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:
RCV002418904.2

Allele description [Variation Report for NM_000321.3(RB1):c.1997G>T (p.Cys666Phe)]

NM_000321.3(RB1):c.1997G>T (p.Cys666Phe)

Gene:
RB1:RB transcriptional corepressor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q14.2
Genomic location:
Preferred name:
NM_000321.3(RB1):c.1997G>T (p.Cys666Phe)
HGVS:
  • NC_000013.11:g.48459724G>T
  • NG_009009.1:g.160978G>T
  • NM_000321.3:c.1997G>TMANE SELECT
  • NP_000312.2:p.Cys666Phe
  • LRG_517t1:c.1997G>T
  • LRG_517:g.160978G>T
  • NC_000013.10:g.49033860G>T
  • NM_000321.2:c.1997G>T
Protein change:
C666F
Links:
dbSNP: rs1160394123
NCBI 1000 Genomes Browser:
rs1160394123
Molecular consequence:
  • NM_000321.3:c.1997G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002720050Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Oct 17, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

Pritchard AL, Johansson PA, Nathan V, Howlie M, Symmons J, Palmer JM, Hayward NK.

PLoS One. 2018;13(4):e0194098. doi: 10.1371/journal.pone.0194098.

PubMed [citation]
PMID:
29641532
PMCID:
PMC5894988

Details of each submission

From Ambry Genetics, SCV002720050.2

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

Description

The p.C666F variant (also known as c.1997G>T), located in coding exon 20 of the RB1 gene, results from a G to T substitution at nucleotide position 1997. The cysteine at codon 666 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024