For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu1559Argfs*15) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4674dup (p.Glu1559fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(2)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4674dup (p.Glu1559fs)
Variation ID: 838793 Accession: VCV000838793.9
- Type and length
-
Duplication, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43074331-43074332 (GRCh38) [ NCBI UCSC ] 17: 41226348-41226349 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 15, 2020 May 1, 2024 Jul 20, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4674dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1559fs frameshift NM_001407571.1:c.4461dup NP_001394500.1:p.Glu1488Argfs frameshift NM_001407581.1:c.4740dup NP_001394510.1:p.Glu1581Argfs frameshift NM_001407582.1:c.4740dup NP_001394511.1:p.Glu1581Argfs frameshift NM_001407583.1:c.4737dup NP_001394512.1:p.Glu1580Argfs frameshift NM_001407585.1:c.4737dup NP_001394514.1:p.Glu1580Argfs frameshift NM_001407587.1:c.4737dup NP_001394516.1:p.Glu1580Argfs frameshift NM_001407590.1:c.4734dup NP_001394519.1:p.Glu1579Argfs frameshift NM_001407591.1:c.4734dup NP_001394520.1:p.Glu1579Argfs frameshift NM_001407593.1:c.4674dup NP_001394522.1:p.Glu1559Argfs frameshift NM_001407594.1:c.4674dup NP_001394523.1:p.Glu1559Argfs frameshift NM_001407596.1:c.4674dup NP_001394525.1:p.Glu1559Argfs frameshift NM_001407597.1:c.4674dup NP_001394526.1:p.Glu1559Argfs frameshift NM_001407598.1:c.4674dup NP_001394527.1:p.Glu1559Argfs frameshift NM_001407602.1:c.4674dup NP_001394531.1:p.Glu1559Argfs frameshift NM_001407603.1:c.4674dup NP_001394532.1:p.Glu1559Argfs frameshift NM_001407605.1:c.4674dup NP_001394534.1:p.Glu1559Argfs frameshift NM_001407610.1:c.4671dup NP_001394539.1:p.Glu1558Argfs frameshift NM_001407611.1:c.4671dup NP_001394540.1:p.Glu1558Argfs frameshift NM_001407612.1:c.4671dup NP_001394541.1:p.Glu1558Argfs frameshift NM_001407613.1:c.4671dup NP_001394542.1:p.Glu1558Argfs frameshift NM_001407614.1:c.4671dup NP_001394543.1:p.Glu1558Argfs frameshift NM_001407615.1:c.4671dup NP_001394544.1:p.Glu1558Argfs frameshift NM_001407616.1:c.4671dup NP_001394545.1:p.Glu1558Argfs frameshift NM_001407617.1:c.4671dup NP_001394546.1:p.Glu1558Argfs frameshift NM_001407618.1:c.4671dup NP_001394547.1:p.Glu1558Argfs frameshift NM_001407619.1:c.4671dup NP_001394548.1:p.Glu1558Argfs frameshift NM_001407620.1:c.4671dup NP_001394549.1:p.Glu1558Argfs frameshift NM_001407621.1:c.4671dup NP_001394550.1:p.Glu1558Argfs frameshift NM_001407622.1:c.4671dup NP_001394551.1:p.Glu1558Argfs frameshift NM_001407623.1:c.4671dup NP_001394552.1:p.Glu1558Argfs frameshift NM_001407624.1:c.4671dup NP_001394553.1:p.Glu1558Argfs frameshift NM_001407625.1:c.4671dup NP_001394554.1:p.Glu1558Argfs frameshift NM_001407626.1:c.4671dup NP_001394555.1:p.Glu1558Argfs frameshift NM_001407627.1:c.4668dup NP_001394556.1:p.Glu1557Argfs frameshift NM_001407628.1:c.4668dup NP_001394557.1:p.Glu1557Argfs frameshift NM_001407629.1:c.4668dup NP_001394558.1:p.Glu1557Argfs frameshift NM_001407630.1:c.4668dup NP_001394559.1:p.Glu1557Argfs frameshift NM_001407631.1:c.4668dup NP_001394560.1:p.Glu1557Argfs frameshift NM_001407632.1:c.4668dup NP_001394561.1:p.Glu1557Argfs frameshift NM_001407633.1:c.4668dup NP_001394562.1:p.Glu1557Argfs frameshift NM_001407634.1:c.4668dup NP_001394563.1:p.Glu1557Argfs frameshift NM_001407635.1:c.4668dup NP_001394564.1:p.Glu1557Argfs frameshift NM_001407636.1:c.4668dup NP_001394565.1:p.Glu1557Argfs frameshift NM_001407637.1:c.4668dup NP_001394566.1:p.Glu1557Argfs frameshift NM_001407638.1:c.4668dup NP_001394567.1:p.Glu1557Argfs frameshift NM_001407639.1:c.4668dup NP_001394568.1:p.Glu1557Argfs frameshift NM_001407640.1:c.4668dup NP_001394569.1:p.Glu1557Argfs frameshift NM_001407641.1:c.4668dup NP_001394570.1:p.Glu1557Argfs frameshift NM_001407642.1:c.4668dup NP_001394571.1:p.Glu1557Argfs frameshift NM_001407644.1:c.4665dup NP_001394573.1:p.Glu1556Argfs frameshift NM_001407645.1:c.4665dup NP_001394574.1:p.Glu1556Argfs frameshift NM_001407646.1:c.4662dup NP_001394575.1:p.Glu1555Argfs frameshift NM_001407647.1:c.4659dup NP_001394576.1:p.Glu1554Argfs frameshift NM_001407648.1:c.4617dup NP_001394577.1:p.Glu1540Argfs frameshift NM_001407649.1:c.4614dup NP_001394578.1:p.Glu1539Argfs frameshift NM_001407652.1:c.4674dup NP_001394581.1:p.Glu1559Argfs frameshift NM_001407653.1:c.4596dup NP_001394582.1:p.Glu1533Argfs frameshift NM_001407654.1:c.4596dup NP_001394583.1:p.Glu1533Argfs frameshift NM_001407655.1:c.4596dup NP_001394584.1:p.Glu1533Argfs frameshift NM_001407656.1:c.4593dup NP_001394585.1:p.Glu1532Argfs frameshift NM_001407657.1:c.4593dup NP_001394586.1:p.Glu1532Argfs frameshift NM_001407658.1:c.4593dup NP_001394587.1:p.Glu1532Argfs frameshift NM_001407659.1:c.4590dup NP_001394588.1:p.Glu1531Argfs frameshift NM_001407660.1:c.4590dup NP_001394589.1:p.Glu1531Argfs frameshift NM_001407661.1:c.4590dup NP_001394590.1:p.Glu1531Argfs frameshift NM_001407662.1:c.4590dup NP_001394591.1:p.Glu1531Argfs frameshift NM_001407663.1:c.4590dup NP_001394592.1:p.Glu1531Argfs frameshift NM_001407664.1:c.4551dup NP_001394593.1:p.Glu1518Argfs frameshift NM_001407665.1:c.4551dup NP_001394594.1:p.Glu1518Argfs frameshift NM_001407666.1:c.4551dup NP_001394595.1:p.Glu1518Argfs frameshift NM_001407667.1:c.4551dup NP_001394596.1:p.Glu1518Argfs frameshift NM_001407668.1:c.4551dup NP_001394597.1:p.Glu1518Argfs frameshift NM_001407669.1:c.4551dup NP_001394598.1:p.Glu1518Argfs frameshift NM_001407670.1:c.4548dup NP_001394599.1:p.Glu1517Argfs frameshift NM_001407671.1:c.4548dup NP_001394600.1:p.Glu1517Argfs frameshift NM_001407672.1:c.4548dup NP_001394601.1:p.Glu1517Argfs frameshift NM_001407673.1:c.4548dup NP_001394602.1:p.Glu1517Argfs frameshift NM_001407674.1:c.4548dup NP_001394603.1:p.Glu1517Argfs frameshift NM_001407675.1:c.4548dup NP_001394604.1:p.Glu1517Argfs frameshift NM_001407676.1:c.4548dup NP_001394605.1:p.Glu1517Argfs frameshift NM_001407677.1:c.4548dup NP_001394606.1:p.Glu1517Argfs frameshift NM_001407678.1:c.4548dup NP_001394607.1:p.Glu1517Argfs frameshift NM_001407679.1:c.4548dup NP_001394608.1:p.Glu1517Argfs frameshift NM_001407680.1:c.4548dup NP_001394609.1:p.Glu1517Argfs frameshift NM_001407681.1:c.4545dup NP_001394610.1:p.Glu1516Argfs frameshift NM_001407682.1:c.4545dup NP_001394611.1:p.Glu1516Argfs frameshift NM_001407683.1:c.4545dup NP_001394612.1:p.Glu1516Argfs frameshift NM_001407684.1:c.4674dup NP_001394613.1:p.Glu1559Argfs frameshift NM_001407685.1:c.4545dup NP_001394614.1:p.Glu1516Argfs frameshift NM_001407686.1:c.4545dup NP_001394615.1:p.Glu1516Argfs frameshift NM_001407687.1:c.4545dup NP_001394616.1:p.Glu1516Argfs frameshift NM_001407688.1:c.4545dup NP_001394617.1:p.Glu1516Argfs frameshift NM_001407689.1:c.4545dup NP_001394618.1:p.Glu1516Argfs frameshift NM_001407690.1:c.4542dup NP_001394619.1:p.Glu1515Argfs frameshift NM_001407691.1:c.4542dup NP_001394620.1:p.Glu1515Argfs frameshift NM_001407692.1:c.4533dup NP_001394621.1:p.Glu1512Argfs frameshift NM_001407694.1:c.4533dup NP_001394623.1:p.Glu1512Argfs frameshift NM_001407695.1:c.4533dup NP_001394624.1:p.Glu1512Argfs frameshift NM_001407696.1:c.4533dup NP_001394625.1:p.Glu1512Argfs frameshift NM_001407697.1:c.4533dup NP_001394626.1:p.Glu1512Argfs frameshift NM_001407698.1:c.4533dup NP_001394627.1:p.Glu1512Argfs frameshift NM_001407724.1:c.4533dup NP_001394653.1:p.Glu1512Argfs frameshift NM_001407725.1:c.4533dup NP_001394654.1:p.Glu1512Argfs frameshift NM_001407726.1:c.4533dup NP_001394655.1:p.Glu1512Argfs frameshift NM_001407727.1:c.4533dup NP_001394656.1:p.Glu1512Argfs frameshift NM_001407728.1:c.4533dup NP_001394657.1:p.Glu1512Argfs frameshift NM_001407729.1:c.4533dup NP_001394658.1:p.Glu1512Argfs frameshift NM_001407730.1:c.4533dup NP_001394659.1:p.Glu1512Argfs frameshift NM_001407731.1:c.4533dup NP_001394660.1:p.Glu1512Argfs frameshift NM_001407732.1:c.4530dup NP_001394661.1:p.Glu1511Argfs frameshift NM_001407733.1:c.4530dup NP_001394662.1:p.Glu1511Argfs frameshift NM_001407734.1:c.4530dup NP_001394663.1:p.Glu1511Argfs frameshift NM_001407735.1:c.4530dup NP_001394664.1:p.Glu1511Argfs frameshift NM_001407736.1:c.4530dup NP_001394665.1:p.Glu1511Argfs frameshift NM_001407737.1:c.4530dup NP_001394666.1:p.Glu1511Argfs frameshift NM_001407738.1:c.4530dup NP_001394667.1:p.Glu1511Argfs frameshift NM_001407739.1:c.4530dup NP_001394668.1:p.Glu1511Argfs frameshift NM_001407740.1:c.4530dup NP_001394669.1:p.Glu1511Argfs frameshift NM_001407741.1:c.4530dup NP_001394670.1:p.Glu1511Argfs frameshift NM_001407742.1:c.4530dup NP_001394671.1:p.Glu1511Argfs frameshift NM_001407743.1:c.4530dup NP_001394672.1:p.Glu1511Argfs frameshift NM_001407744.1:c.4530dup NP_001394673.1:p.Glu1511Argfs frameshift NM_001407745.1:c.4530dup NP_001394674.1:p.Glu1511Argfs frameshift NM_001407746.1:c.4530dup NP_001394675.1:p.Glu1511Argfs frameshift NM_001407747.1:c.4530dup NP_001394676.1:p.Glu1511Argfs frameshift NM_001407748.1:c.4530dup NP_001394677.1:p.Glu1511Argfs frameshift NM_001407749.1:c.4530dup NP_001394678.1:p.Glu1511Argfs frameshift NM_001407750.1:c.4530dup NP_001394679.1:p.Glu1511Argfs frameshift NM_001407751.1:c.4530dup NP_001394680.1:p.Glu1511Argfs frameshift NM_001407752.1:c.4530dup NP_001394681.1:p.Glu1511Argfs frameshift NM_001407838.1:c.4527dup NP_001394767.1:p.Glu1510Argfs frameshift NM_001407839.1:c.4527dup NP_001394768.1:p.Glu1510Argfs frameshift NM_001407841.1:c.4527dup NP_001394770.1:p.Glu1510Argfs frameshift NM_001407842.1:c.4527dup NP_001394771.1:p.Glu1510Argfs frameshift NM_001407843.1:c.4527dup NP_001394772.1:p.Glu1510Argfs frameshift NM_001407844.1:c.4527dup NP_001394773.1:p.Glu1510Argfs frameshift NM_001407845.1:c.4527dup NP_001394774.1:p.Glu1510Argfs frameshift NM_001407846.1:c.4527dup NP_001394775.1:p.Glu1510Argfs frameshift NM_001407847.1:c.4527dup NP_001394776.1:p.Glu1510Argfs frameshift NM_001407848.1:c.4527dup NP_001394777.1:p.Glu1510Argfs frameshift NM_001407849.1:c.4527dup NP_001394778.1:p.Glu1510Argfs frameshift NM_001407850.1:c.4527dup NP_001394779.1:p.Glu1510Argfs frameshift NM_001407851.1:c.4527dup NP_001394780.1:p.Glu1510Argfs frameshift NM_001407852.1:c.4527dup NP_001394781.1:p.Glu1510Argfs frameshift NM_001407853.1:c.4527dup NP_001394782.1:p.Glu1510Argfs frameshift NM_001407854.1:c.4674dup NP_001394783.1:p.Glu1559Argfs frameshift NM_001407858.1:c.4671dup NP_001394787.1:p.Glu1558Argfs frameshift NM_001407859.1:c.4671dup NP_001394788.1:p.Glu1558Argfs frameshift NM_001407860.1:c.4671dup NP_001394789.1:p.Glu1558Argfs frameshift NM_001407861.1:c.4668dup NP_001394790.1:p.Glu1557Argfs frameshift NM_001407862.1:c.4473dup NP_001394791.1:p.Glu1492Argfs frameshift NM_001407863.1:c.4548dup NP_001394792.1:p.Glu1517Argfs frameshift NM_001407874.1:c.4467dup NP_001394803.1:p.Glu1490Argfs frameshift NM_001407875.1:c.4467dup NP_001394804.1:p.Glu1490Argfs frameshift NM_001407879.1:c.4464dup NP_001394808.1:p.Glu1489Argfs frameshift NM_001407881.1:c.4464dup NP_001394810.1:p.Glu1489Argfs frameshift NM_001407882.1:c.4464dup NP_001394811.1:p.Glu1489Argfs frameshift NM_001407884.1:c.4464dup NP_001394813.1:p.Glu1489Argfs frameshift NM_001407885.1:c.4464dup NP_001394814.1:p.Glu1489Argfs frameshift NM_001407886.1:c.4464dup NP_001394815.1:p.Glu1489Argfs frameshift NM_001407887.1:c.4464dup NP_001394816.1:p.Glu1489Argfs frameshift NM_001407889.1:c.4464dup NP_001394818.1:p.Glu1489Argfs frameshift NM_001407894.1:c.4461dup NP_001394823.1:p.Glu1488Argfs frameshift NM_001407895.1:c.4461dup NP_001394824.1:p.Glu1488Argfs frameshift NM_001407896.1:c.4461dup NP_001394825.1:p.Glu1488Argfs frameshift NM_001407897.1:c.4461dup NP_001394826.1:p.Glu1488Argfs frameshift NM_001407898.1:c.4461dup NP_001394827.1:p.Glu1488Argfs frameshift NM_001407899.1:c.4461dup NP_001394828.1:p.Glu1488Argfs frameshift NM_001407900.1:c.4461dup NP_001394829.1:p.Glu1488Argfs frameshift NM_001407902.1:c.4461dup NP_001394831.1:p.Glu1488Argfs frameshift NM_001407904.1:c.4461dup NP_001394833.1:p.Glu1488Argfs frameshift NM_001407906.1:c.4461dup NP_001394835.1:p.Glu1488Argfs frameshift NM_001407907.1:c.4461dup NP_001394836.1:p.Glu1488Argfs frameshift NM_001407908.1:c.4461dup NP_001394837.1:p.Glu1488Argfs frameshift NM_001407909.1:c.4461dup NP_001394838.1:p.Glu1488Argfs frameshift NM_001407910.1:c.4461dup NP_001394839.1:p.Glu1488Argfs frameshift NM_001407915.1:c.4458dup NP_001394844.1:p.Glu1487Argfs frameshift NM_001407916.1:c.4458dup NP_001394845.1:p.Glu1487Argfs frameshift NM_001407917.1:c.4458dup NP_001394846.1:p.Glu1487Argfs frameshift NM_001407918.1:c.4458dup NP_001394847.1:p.Glu1487Argfs frameshift NM_001407919.1:c.4551dup NP_001394848.1:p.Glu1518Argfs frameshift NM_001407920.1:c.4410dup NP_001394849.1:p.Glu1471Argfs frameshift NM_001407921.1:c.4410dup NP_001394850.1:p.Glu1471Argfs frameshift NM_001407922.1:c.4410dup NP_001394851.1:p.Glu1471Argfs frameshift NM_001407923.1:c.4410dup NP_001394852.1:p.Glu1471Argfs frameshift NM_001407924.1:c.4410dup NP_001394853.1:p.Glu1471Argfs frameshift NM_001407925.1:c.4410dup NP_001394854.1:p.Glu1471Argfs frameshift NM_001407926.1:c.4410dup NP_001394855.1:p.Glu1471Argfs frameshift NM_001407927.1:c.4407dup NP_001394856.1:p.Glu1470Argfs frameshift NM_001407928.1:c.4407dup NP_001394857.1:p.Glu1470Argfs frameshift NM_001407929.1:c.4407dup NP_001394858.1:p.Glu1470Argfs frameshift NM_001407930.1:c.4407dup NP_001394859.1:p.Glu1470Argfs frameshift NM_001407931.1:c.4407dup NP_001394860.1:p.Glu1470Argfs frameshift NM_001407932.1:c.4407dup NP_001394861.1:p.Glu1470Argfs frameshift NM_001407933.1:c.4407dup NP_001394862.1:p.Glu1470Argfs frameshift NM_001407934.1:c.4404dup NP_001394863.1:p.Glu1469Argfs frameshift NM_001407935.1:c.4404dup NP_001394864.1:p.Glu1469Argfs frameshift NM_001407936.1:c.4404dup NP_001394865.1:p.Glu1469Argfs frameshift NM_001407937.1:c.4551dup NP_001394866.1:p.Glu1518Argfs frameshift NM_001407938.1:c.4551dup NP_001394867.1:p.Glu1518Argfs frameshift NM_001407939.1:c.4548dup NP_001394868.1:p.Glu1517Argfs frameshift NM_001407940.1:c.4548dup NP_001394869.1:p.Glu1517Argfs frameshift NM_001407941.1:c.4545dup NP_001394870.1:p.Glu1516Argfs frameshift NM_001407942.1:c.4533dup NP_001394871.1:p.Glu1512Argfs frameshift NM_001407943.1:c.4530dup NP_001394872.1:p.Glu1511Argfs frameshift NM_001407944.1:c.4530dup NP_001394873.1:p.Glu1511Argfs frameshift NM_001407945.1:c.4530dup NP_001394874.1:p.Glu1511Argfs frameshift NM_001407946.1:c.4341dup NP_001394875.1:p.Glu1448Argfs frameshift NM_001407947.1:c.4341dup NP_001394876.1:p.Glu1448Argfs frameshift NM_001407948.1:c.4341dup NP_001394877.1:p.Glu1448Argfs frameshift NM_001407949.1:c.4341dup NP_001394878.1:p.Glu1448Argfs frameshift NM_001407950.1:c.4338dup NP_001394879.1:p.Glu1447Argfs frameshift NM_001407951.1:c.4338dup NP_001394880.1:p.Glu1447Argfs frameshift NM_001407952.1:c.4338dup NP_001394881.1:p.Glu1447Argfs frameshift NM_001407953.1:c.4338dup NP_001394882.1:p.Glu1447Argfs frameshift NM_001407954.1:c.4338dup NP_001394883.1:p.Glu1447Argfs frameshift NM_001407955.1:c.4338dup NP_001394884.1:p.Glu1447Argfs frameshift NM_001407956.1:c.4335dup NP_001394885.1:p.Glu1446Argfs frameshift NM_001407957.1:c.4335dup NP_001394886.1:p.Glu1446Argfs frameshift NM_001407958.1:c.4335dup NP_001394887.1:p.Glu1446Argfs frameshift NM_001407959.1:c.4293dup NP_001394888.1:p.Glu1432Argfs frameshift NM_001407960.1:c.4290dup NP_001394889.1:p.Glu1431Argfs frameshift NM_001407962.1:c.4290dup NP_001394891.1:p.Glu1431Argfs frameshift NM_001407963.1:c.4287dup NP_001394892.1:p.Glu1430Argfs frameshift NM_001407965.1:c.4167dup NP_001394894.1:p.Glu1390Argfs frameshift NM_001407966.1:c.3786dup NP_001394895.1:p.Glu1263Argfs frameshift NM_001407967.1:c.3783dup NP_001394896.1:p.Glu1262Argfs frameshift NM_001407968.1:c.2070dup NP_001394897.1:p.Glu691Argfs frameshift NM_001407969.1:c.2067dup NP_001394898.1:p.Glu690Argfs frameshift NM_001407970.1:c.1431dup NP_001394899.1:p.Glu478Argfs frameshift NM_001407971.1:c.1431dup NP_001394900.1:p.Glu478Argfs frameshift NM_001407972.1:c.1428dup NP_001394901.1:p.Glu477Argfs frameshift NM_001407973.1:c.1365dup NP_001394902.1:p.Glu456Argfs frameshift NM_001407974.1:c.1365dup NP_001394903.1:p.Glu456Argfs frameshift NM_001407975.1:c.1365dup NP_001394904.1:p.Glu456Argfs frameshift NM_001407976.1:c.1365dup NP_001394905.1:p.Glu456Argfs frameshift NM_001407977.1:c.1365dup NP_001394906.1:p.Glu456Argfs frameshift NM_001407978.1:c.1365dup NP_001394907.1:p.Glu456Argfs frameshift NM_001407979.1:c.1362dup NP_001394908.1:p.Glu455Argfs frameshift NM_001407980.1:c.1362dup NP_001394909.1:p.Glu455Argfs frameshift NM_001407981.1:c.1362dup NP_001394910.1:p.Glu455Argfs frameshift NM_001407982.1:c.1362dup NP_001394911.1:p.Glu455Argfs frameshift NM_001407983.1:c.1362dup NP_001394912.1:p.Glu455Argfs frameshift NM_001407984.1:c.1362dup NP_001394913.1:p.Glu455Argfs frameshift NM_001407985.1:c.1362dup NP_001394914.1:p.Glu455Argfs frameshift NM_001407986.1:c.1362dup NP_001394915.1:p.Glu455Argfs frameshift NM_001407990.1:c.1362dup NP_001394919.1:p.Glu455Argfs frameshift NM_001407991.1:c.1362dup NP_001394920.1:p.Glu455Argfs frameshift NM_001407992.1:c.1362dup NP_001394921.1:p.Glu455Argfs frameshift NM_001407993.1:c.1362dup NP_001394922.1:p.Glu455Argfs frameshift NM_001408392.1:c.1359dup NP_001395321.1:p.Glu454Argfs frameshift NM_001408396.1:c.1359dup NP_001395325.1:p.Glu454Argfs frameshift NM_001408397.1:c.1359dup NP_001395326.1:p.Glu454Argfs frameshift NM_001408398.1:c.1359dup NP_001395327.1:p.Glu454Argfs frameshift NM_001408399.1:c.1359dup NP_001395328.1:p.Glu454Argfs frameshift NM_001408400.1:c.1359dup NP_001395329.1:p.Glu454Argfs frameshift NM_001408401.1:c.1359dup NP_001395330.1:p.Glu454Argfs frameshift NM_001408402.1:c.1359dup NP_001395331.1:p.Glu454Argfs frameshift NM_001408403.1:c.1359dup NP_001395332.1:p.Glu454Argfs frameshift NM_001408404.1:c.1359dup NP_001395333.1:p.Glu454Argfs frameshift NM_001408406.1:c.1356dup NP_001395335.1:p.Glu453Argfs frameshift NM_001408407.1:c.1356dup NP_001395336.1:p.Glu453Argfs frameshift NM_001408408.1:c.1356dup NP_001395337.1:p.Glu453Argfs frameshift NM_001408409.1:c.1353dup NP_001395338.1:p.Glu452Argfs frameshift NM_001408410.1:c.1290dup NP_001395339.1:p.Glu431Argfs frameshift NM_001408411.1:c.1287dup NP_001395340.1:p.Glu430Argfs frameshift NM_001408412.1:c.1284dup NP_001395341.1:p.Glu429Argfs frameshift NM_001408413.1:c.1284dup NP_001395342.1:p.Glu429Argfs frameshift NM_001408414.1:c.1284dup NP_001395343.1:p.Glu429Argfs frameshift NM_001408415.1:c.1284dup NP_001395344.1:p.Glu429Argfs frameshift NM_001408416.1:c.1284dup NP_001395345.1:p.Glu429Argfs frameshift NM_001408418.1:c.1248dup NP_001395347.1:p.Glu417Argfs frameshift NM_001408419.1:c.1248dup NP_001395348.1:p.Glu417Argfs frameshift NM_001408420.1:c.1248dup NP_001395349.1:p.Glu417Argfs frameshift NM_001408421.1:c.1245dup NP_001395350.1:p.Glu416Argfs frameshift NM_001408422.1:c.1245dup NP_001395351.1:p.Glu416Argfs frameshift NM_001408423.1:c.1245dup NP_001395352.1:p.Glu416Argfs frameshift NM_001408424.1:c.1245dup NP_001395353.1:p.Glu416Argfs frameshift NM_001408425.1:c.1242dup NP_001395354.1:p.Glu415Argfs frameshift NM_001408426.1:c.1242dup NP_001395355.1:p.Glu415Argfs frameshift NM_001408427.1:c.1242dup NP_001395356.1:p.Glu415Argfs frameshift NM_001408428.1:c.1242dup NP_001395357.1:p.Glu415Argfs frameshift NM_001408429.1:c.1242dup NP_001395358.1:p.Glu415Argfs frameshift NM_001408430.1:c.1242dup NP_001395359.1:p.Glu415Argfs frameshift NM_001408431.1:c.1242dup NP_001395360.1:p.Glu415Argfs frameshift NM_001408432.1:c.1239dup NP_001395361.1:p.Glu414Argfs frameshift NM_001408433.1:c.1239dup NP_001395362.1:p.Glu414Argfs frameshift NM_001408434.1:c.1239dup NP_001395363.1:p.Glu414Argfs frameshift NM_001408435.1:c.1239dup NP_001395364.1:p.Glu414Argfs frameshift NM_001408436.1:c.1239dup NP_001395365.1:p.Glu414Argfs frameshift NM_001408437.1:c.1239dup NP_001395366.1:p.Glu414Argfs frameshift NM_001408438.1:c.1239dup NP_001395367.1:p.Glu414Argfs frameshift NM_001408439.1:c.1239dup NP_001395368.1:p.Glu414Argfs frameshift NM_001408440.1:c.1239dup NP_001395369.1:p.Glu414Argfs frameshift NM_001408441.1:c.1239dup NP_001395370.1:p.Glu414Argfs frameshift NM_001408442.1:c.1239dup NP_001395371.1:p.Glu414Argfs frameshift NM_001408443.1:c.1239dup NP_001395372.1:p.Glu414Argfs frameshift NM_001408444.1:c.1239dup NP_001395373.1:p.Glu414Argfs frameshift NM_001408445.1:c.1236dup NP_001395374.1:p.Glu413Argfs frameshift NM_001408446.1:c.1236dup NP_001395375.1:p.Glu413Argfs frameshift NM_001408447.1:c.1236dup NP_001395376.1:p.Glu413Argfs frameshift NM_001408448.1:c.1236dup NP_001395377.1:p.Glu413Argfs frameshift NM_001408450.1:c.1236dup NP_001395379.1:p.Glu413Argfs frameshift NM_001408451.1:c.1230dup NP_001395380.1:p.Glu411Argfs frameshift NM_001408452.1:c.1224dup NP_001395381.1:p.Glu409Argfs frameshift NM_001408453.1:c.1224dup NP_001395382.1:p.Glu409Argfs frameshift NM_001408454.1:c.1224dup NP_001395383.1:p.Glu409Argfs frameshift NM_001408455.1:c.1224dup NP_001395384.1:p.Glu409Argfs frameshift NM_001408456.1:c.1224dup NP_001395385.1:p.Glu409Argfs frameshift NM_001408457.1:c.1224dup NP_001395386.1:p.Glu409Argfs frameshift NM_001408458.1:c.1221dup NP_001395387.1:p.Glu408Argfs frameshift NM_001408459.1:c.1221dup NP_001395388.1:p.Glu408Argfs frameshift NM_001408460.1:c.1221dup NP_001395389.1:p.Glu408Argfs frameshift NM_001408461.1:c.1221dup NP_001395390.1:p.Glu408Argfs frameshift NM_001408462.1:c.1221dup NP_001395391.1:p.Glu408Argfs frameshift NM_001408463.1:c.1221dup NP_001395392.1:p.Glu408Argfs frameshift NM_001408464.1:c.1221dup NP_001395393.1:p.Glu408Argfs frameshift NM_001408465.1:c.1221dup NP_001395394.1:p.Glu408Argfs frameshift NM_001408466.1:c.1221dup NP_001395395.1:p.Glu408Argfs frameshift NM_001408467.1:c.1221dup NP_001395396.1:p.Glu408Argfs frameshift NM_001408468.1:c.1218dup NP_001395397.1:p.Glu407Argfs frameshift NM_001408469.1:c.1218dup NP_001395398.1:p.Glu407Argfs frameshift NM_001408470.1:c.1218dup NP_001395399.1:p.Glu407Argfs frameshift NM_001408472.1:c.1362dup NP_001395401.1:p.Glu455Argfs frameshift NM_001408473.1:c.1359dup NP_001395402.1:p.Glu454Argfs frameshift NM_001408474.1:c.1164dup NP_001395403.1:p.Glu389Argfs frameshift NM_001408475.1:c.1161dup NP_001395404.1:p.Glu388Argfs frameshift NM_001408476.1:c.1161dup NP_001395405.1:p.Glu388Argfs frameshift NM_001408478.1:c.1155dup NP_001395407.1:p.Glu386Argfs frameshift NM_001408479.1:c.1155dup NP_001395408.1:p.Glu386Argfs frameshift NM_001408480.1:c.1155dup NP_001395409.1:p.Glu386Argfs frameshift NM_001408481.1:c.1152dup NP_001395410.1:p.Glu385Argfs frameshift NM_001408482.1:c.1152dup NP_001395411.1:p.Glu385Argfs frameshift NM_001408483.1:c.1152dup NP_001395412.1:p.Glu385Argfs frameshift NM_001408484.1:c.1152dup NP_001395413.1:p.Glu385Argfs frameshift NM_001408485.1:c.1152dup NP_001395414.1:p.Glu385Argfs frameshift NM_001408489.1:c.1152dup NP_001395418.1:p.Glu385Argfs frameshift NM_001408490.1:c.1152dup NP_001395419.1:p.Glu385Argfs frameshift NM_001408491.1:c.1152dup NP_001395420.1:p.Glu385Argfs frameshift NM_001408492.1:c.1149dup NP_001395421.1:p.Glu384Argfs frameshift NM_001408493.1:c.1149dup NP_001395422.1:p.Glu384Argfs frameshift NM_001408494.1:c.1125dup NP_001395423.1:p.Glu376Argfs frameshift NM_001408495.1:c.1119dup NP_001395424.1:p.Glu374Argfs frameshift NM_001408496.1:c.1101dup NP_001395425.1:p.Glu368Argfs frameshift NM_001408497.1:c.1101dup NP_001395426.1:p.Glu368Argfs frameshift NM_001408498.1:c.1101dup NP_001395427.1:p.Glu368Argfs frameshift NM_001408499.1:c.1101dup NP_001395428.1:p.Glu368Argfs frameshift NM_001408500.1:c.1101dup NP_001395429.1:p.Glu368Argfs frameshift NM_001408501.1:c.1101dup NP_001395430.1:p.Glu368Argfs frameshift NM_001408502.1:c.1098dup NP_001395431.1:p.Glu367Argfs frameshift NM_001408503.1:c.1098dup NP_001395432.1:p.Glu367Argfs frameshift NM_001408504.1:c.1098dup NP_001395433.1:p.Glu367Argfs frameshift NM_001408505.1:c.1095dup NP_001395434.1:p.Glu366Argfs frameshift NM_001408506.1:c.1038dup NP_001395435.1:p.Glu347Argfs frameshift NM_001408507.1:c.1035dup NP_001395436.1:p.Glu346Argfs frameshift NM_001408508.1:c.1026dup NP_001395437.1:p.Glu343Argfs frameshift NM_001408509.1:c.1023dup NP_001395438.1:p.Glu342Argfs frameshift NM_001408510.1:c.984dup NP_001395439.1:p.Glu329Argfs frameshift NM_001408511.1:c.981dup NP_001395440.1:p.Glu328Argfs frameshift NM_001408512.1:c.861dup NP_001395441.1:p.Glu288Argfs frameshift NM_007294.3:c.4674dupA NM_007297.4:c.4533dup NP_009228.2:p.Glu1512fs frameshift NM_007298.4:c.1362dup NP_009229.2:p.Glu455Argfs frameshift NM_007299.4:c.1362dup NP_009230.2:p.Glu455fs frameshift NM_007300.4:c.4737dup NP_009231.2:p.Glu1580fs frameshift NM_007304.2:c.1362dup NP_009235.2:p.Glu455Argfs frameshift NR_027676.2:n.4851dup non-coding transcript variant NC_000017.11:g.43074332dup NC_000017.10:g.41226349dup NG_005905.2:g.143652dup LRG_292:g.143652dup LRG_292t1:c.4674dup LRG_292p1:p.Glu1559Argfs - Protein change
- E1580fs, E1512fs, E1559fs, E455fs
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074331:T:TT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13040 | 14846 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 3, 2019 | RCV001040412.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 20, 2023 | RCV003339438.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Dec 03, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001203986.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has not … (more)
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu1559Argfs*15) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. (less)
|
|
|
Pathogenic
(Jul 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV004058423.2
First in ClinVar: Oct 28, 2023 Last updated: May 01, 2024 |
Comment:
The c.4674dupA pathogenic mutation, located in coding exon 13 of the BRCA1 gene, results from a duplication of A at nucleotide position 4674, causing a … (more)
The c.4674dupA pathogenic mutation, located in coding exon 13 of the BRCA1 gene, results from a duplication of A at nucleotide position 4674, causing a translational frameshift with a predicted alternate stop codon (p.E1559Rfs*15). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
Comment:
Comment:
The c.4674dupA pathogenic mutation, located in coding exon 13 of the BRCA1 gene, results from a duplication of A at nucleotide position 4674, causing a translational frameshift with a predicted alternate stop codon (p.E1559Rfs*15). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu1559Argfs*15) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Comment:
The c.4674dupA pathogenic mutation, located in coding exon 13 of the BRCA1 gene, results from a duplication of A at nucleotide position 4674, causing a translational frameshift with a predicted alternate stop codon (p.E1559Rfs*15). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
Text-mined citations for rs2052585246 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.