NM_000179.2(MSH6):c.1998_1999delTG (p.Asp667Phefs) AND not provided

Clinical significance:Pathogenic (Last evaluated: Aug 14, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000481527.1

Allele description

NM_000179.2(MSH6):c.1998_1999delTG (p.Asp667Phefs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.1998_1999delTG (p.Asp667Phefs)
HGVS:
  • NC_000002.12:g.47799981_47799982delTG
  • NM_000179.2:c.1998_1999delTG
  • NP_000170.1:p.Asp667Phefs
  • LRG_219t1:c.1998_1999del
  • LRG_219:g.21835_21836del
  • LRG_219p1:p.Asp667Phefs
  • NC_000002.11:g.48027120_48027121delTG
Links:
dbSNP: rs1064794028
NCBI 1000 Genomes Browser:
rs1064794028
Molecular consequence:
  • NM_000179.2:c.1998_1999delTG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000567626GeneDxcriteria provided, single submitter
Pathogenic
(Aug 14, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000567626.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is denoted BRCA1 c.189A>T at the cDNA level, p.Leu63Phe (L63F) at the protein level, and results in the change of a Leucine to a Phenylalanine (TTA>TTT). Using alternate nomenclature, this variant would be defined as BRCA1 308A>T. This variant is reported to have been observed in at least one individual with breast and/or ovarian cancer (Brzovic 2001). Additionally, BRCA1 Leu63Phe has been shown to result in reduced ubiquitin ligase activity of the BRCA1/BARD1 heterodimer and to impair the ability of BRCA1 to repress ER-alpha activity compared to the wild-type controls (Brzovic 2003, Ma 2005). BRCA1 Leu63Phe was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Leucine and Phenylalanine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Leu63Phe occurs at a position that is conserved across species and is located in the RING-type Zinc finger domain and a region known to interact with multiple other proteins (Borg 2010, Paul 2014), In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BRCA1 Leu63Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.

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

Last Updated: Mar 30, 2019

Support Center