This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 1396 of the BRCA1 protein (p.Gln1396Lys). This variant is present in population databases (rs80357011, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 182160). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4186C>A (p.Gln1396Lys)
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.
(3)
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.
Uncertain significance
3
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4186C>A (p.Gln1396Lys)
Variation ID: 182160 Accession: VCV000182160.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43082575 (GRCh38) [ NCBI UCSC ] 17: 41234592 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jul 24, 2016 May 1, 2024 Oct 27, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4186C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln1396Lys missense NM_001407571.1:c.3973C>A NP_001394500.1:p.Gln1325Lys missense NM_001407581.1:c.4186C>A NP_001394510.1:p.Gln1396Lys missense NM_001407582.1:c.4186C>A NP_001394511.1:p.Gln1396Lys missense NM_001407583.1:c.4186C>A NP_001394512.1:p.Gln1396Lys missense NM_001407585.1:c.4186C>A NP_001394514.1:p.Gln1396Lys missense NM_001407587.1:c.4183C>A NP_001394516.1:p.Gln1395Lys missense NM_001407590.1:c.4183C>A NP_001394519.1:p.Gln1395Lys missense NM_001407591.1:c.4183C>A NP_001394520.1:p.Gln1395Lys missense NM_001407593.1:c.4186C>A NP_001394522.1:p.Gln1396Lys missense NM_001407594.1:c.4186C>A NP_001394523.1:p.Gln1396Lys missense NM_001407596.1:c.4186C>A NP_001394525.1:p.Gln1396Lys missense NM_001407597.1:c.4186C>A NP_001394526.1:p.Gln1396Lys missense NM_001407598.1:c.4186C>A NP_001394527.1:p.Gln1396Lys missense NM_001407602.1:c.4186C>A NP_001394531.1:p.Gln1396Lys missense NM_001407603.1:c.4186C>A NP_001394532.1:p.Gln1396Lys missense NM_001407605.1:c.4186C>A NP_001394534.1:p.Gln1396Lys missense NM_001407610.1:c.4183C>A NP_001394539.1:p.Gln1395Lys missense NM_001407611.1:c.4183C>A NP_001394540.1:p.Gln1395Lys missense NM_001407612.1:c.4183C>A NP_001394541.1:p.Gln1395Lys missense NM_001407613.1:c.4183C>A NP_001394542.1:p.Gln1395Lys missense NM_001407614.1:c.4183C>A NP_001394543.1:p.Gln1395Lys missense NM_001407615.1:c.4183C>A NP_001394544.1:p.Gln1395Lys missense NM_001407616.1:c.4186C>A NP_001394545.1:p.Gln1396Lys missense NM_001407617.1:c.4186C>A NP_001394546.1:p.Gln1396Lys missense NM_001407618.1:c.4186C>A NP_001394547.1:p.Gln1396Lys missense NM_001407619.1:c.4186C>A NP_001394548.1:p.Gln1396Lys missense NM_001407620.1:c.4186C>A NP_001394549.1:p.Gln1396Lys missense NM_001407621.1:c.4186C>A NP_001394550.1:p.Gln1396Lys missense NM_001407622.1:c.4186C>A NP_001394551.1:p.Gln1396Lys missense NM_001407623.1:c.4186C>A NP_001394552.1:p.Gln1396Lys missense NM_001407633.1:c.4183C>A NP_001394562.1:p.Gln1395Lys missense NM_001407634.1:c.4183C>A NP_001394563.1:p.Gln1395Lys missense NM_001407635.1:c.4183C>A NP_001394564.1:p.Gln1395Lys missense NM_001407636.1:c.4183C>A NP_001394565.1:p.Gln1395Lys missense NM_001407637.1:c.4183C>A NP_001394566.1:p.Gln1395Lys missense NM_001407638.1:c.4183C>A NP_001394567.1:p.Gln1395Lys missense NM_001407648.1:c.4063C>A NP_001394577.1:p.Gln1355Lys missense NM_001407649.1:c.4060C>A NP_001394578.1:p.Gln1354Lys missense NM_001407652.1:c.4186C>A NP_001394581.1:p.Gln1396Lys missense NM_001407653.1:c.4108C>A NP_001394582.1:p.Gln1370Lys missense NM_001407654.1:c.4108C>A NP_001394583.1:p.Gln1370Lys missense NM_001407655.1:c.4108C>A NP_001394584.1:p.Gln1370Lys missense NM_001407657.1:c.4108C>A NP_001394586.1:p.Gln1370Lys missense NM_001407658.1:c.4108C>A NP_001394587.1:p.Gln1370Lys missense NM_001407661.1:c.4105C>A NP_001394590.1:p.Gln1369Lys missense NM_001407662.1:c.4105C>A NP_001394591.1:p.Gln1369Lys missense NM_001407664.1:c.4063C>A NP_001394593.1:p.Gln1355Lys missense NM_001407665.1:c.4063C>A NP_001394594.1:p.Gln1355Lys missense NM_001407666.1:c.4063C>A NP_001394595.1:p.Gln1355Lys missense NM_001407667.1:c.4063C>A NP_001394596.1:p.Gln1355Lys missense NM_001407668.1:c.4063C>A NP_001394597.1:p.Gln1355Lys missense NM_001407669.1:c.4063C>A NP_001394598.1:p.Gln1355Lys missense NM_001407670.1:c.4060C>A NP_001394599.1:p.Gln1354Lys missense NM_001407671.1:c.4060C>A NP_001394600.1:p.Gln1354Lys missense NM_001407672.1:c.4060C>A NP_001394601.1:p.Gln1354Lys missense NM_001407673.1:c.4060C>A NP_001394602.1:p.Gln1354Lys missense NM_001407677.1:c.4063C>A NP_001394606.1:p.Gln1355Lys missense NM_001407678.1:c.4063C>A NP_001394607.1:p.Gln1355Lys missense NM_001407679.1:c.4063C>A NP_001394608.1:p.Gln1355Lys missense NM_001407680.1:c.4063C>A NP_001394609.1:p.Gln1355Lys missense NM_001407684.1:c.4186C>A NP_001394613.1:p.Gln1396Lys missense NM_001407688.1:c.4060C>A NP_001394617.1:p.Gln1354Lys missense NM_001407689.1:c.4060C>A NP_001394618.1:p.Gln1354Lys missense NM_001407692.1:c.4045C>A NP_001394621.1:p.Gln1349Lys missense NM_001407694.1:c.4045C>A NP_001394623.1:p.Gln1349Lys missense NM_001407695.1:c.4045C>A NP_001394624.1:p.Gln1349Lys missense NM_001407696.1:c.4045C>A NP_001394625.1:p.Gln1349Lys missense NM_001407697.1:c.4045C>A NP_001394626.1:p.Gln1349Lys missense NM_001407698.1:c.4045C>A NP_001394627.1:p.Gln1349Lys missense NM_001407724.1:c.4045C>A NP_001394653.1:p.Gln1349Lys missense NM_001407725.1:c.4045C>A NP_001394654.1:p.Gln1349Lys missense NM_001407726.1:c.4045C>A NP_001394655.1:p.Gln1349Lys missense NM_001407727.1:c.4045C>A NP_001394656.1:p.Gln1349Lys missense NM_001407728.1:c.4045C>A NP_001394657.1:p.Gln1349Lys missense NM_001407729.1:c.4045C>A NP_001394658.1:p.Gln1349Lys missense NM_001407730.1:c.4045C>A NP_001394659.1:p.Gln1349Lys missense NM_001407731.1:c.4045C>A NP_001394660.1:p.Gln1349Lys missense NM_001407732.1:c.4045C>A NP_001394661.1:p.Gln1349Lys missense NM_001407733.1:c.4045C>A NP_001394662.1:p.Gln1349Lys missense NM_001407734.1:c.4045C>A NP_001394663.1:p.Gln1349Lys missense NM_001407735.1:c.4045C>A NP_001394664.1:p.Gln1349Lys missense NM_001407736.1:c.4045C>A NP_001394665.1:p.Gln1349Lys missense NM_001407737.1:c.4045C>A NP_001394666.1:p.Gln1349Lys missense NM_001407738.1:c.4045C>A NP_001394667.1:p.Gln1349Lys missense NM_001407739.1:c.4045C>A NP_001394668.1:p.Gln1349Lys missense NM_001407740.1:c.4042C>A NP_001394669.1:p.Gln1348Lys missense NM_001407741.1:c.4042C>A NP_001394670.1:p.Gln1348Lys missense NM_001407742.1:c.4042C>A NP_001394671.1:p.Gln1348Lys missense NM_001407743.1:c.4042C>A NP_001394672.1:p.Gln1348Lys missense NM_001407744.1:c.4042C>A NP_001394673.1:p.Gln1348Lys missense NM_001407745.1:c.4042C>A NP_001394674.1:p.Gln1348Lys missense NM_001407746.1:c.4042C>A NP_001394675.1:p.Gln1348Lys missense NM_001407747.1:c.4042C>A NP_001394676.1:p.Gln1348Lys missense NM_001407748.1:c.4042C>A NP_001394677.1:p.Gln1348Lys missense NM_001407749.1:c.4042C>A NP_001394678.1:p.Gln1348Lys missense NM_001407838.1:c.4042C>A NP_001394767.1:p.Gln1348Lys missense NM_001407839.1:c.4042C>A NP_001394768.1:p.Gln1348Lys missense NM_001407841.1:c.4042C>A NP_001394770.1:p.Gln1348Lys missense NM_001407842.1:c.4042C>A NP_001394771.1:p.Gln1348Lys missense NM_001407843.1:c.4042C>A NP_001394772.1:p.Gln1348Lys missense NM_001407844.1:c.4042C>A NP_001394773.1:p.Gln1348Lys missense NM_001407845.1:c.4042C>A NP_001394774.1:p.Gln1348Lys missense NM_001407846.1:c.4042C>A NP_001394775.1:p.Gln1348Lys missense NM_001407853.1:c.3973C>A NP_001394782.1:p.Gln1325Lys missense NM_001407854.1:c.4186C>A NP_001394783.1:p.Gln1396Lys missense NM_001407858.1:c.4186C>A NP_001394787.1:p.Gln1396Lys missense NM_001407859.1:c.4186C>A NP_001394788.1:p.Gln1396Lys missense NM_001407860.1:c.4183C>A NP_001394789.1:p.Gln1395Lys missense NM_001407861.1:c.4183C>A NP_001394790.1:p.Gln1395Lys missense NM_001407862.1:c.3985C>A NP_001394791.1:p.Gln1329Lys missense NM_001407863.1:c.4063C>A NP_001394792.1:p.Gln1355Lys missense NM_001407874.1:c.3982C>A NP_001394803.1:p.Gln1328Lys missense NM_001407875.1:c.3982C>A NP_001394804.1:p.Gln1328Lys missense NM_001407879.1:c.3976C>A NP_001394808.1:p.Gln1326Lys missense NM_001407881.1:c.3976C>A NP_001394810.1:p.Gln1326Lys missense NM_001407882.1:c.3976C>A NP_001394811.1:p.Gln1326Lys missense NM_001407884.1:c.3976C>A NP_001394813.1:p.Gln1326Lys missense NM_001407885.1:c.3976C>A NP_001394814.1:p.Gln1326Lys missense NM_001407886.1:c.3976C>A NP_001394815.1:p.Gln1326Lys missense NM_001407887.1:c.3976C>A NP_001394816.1:p.Gln1326Lys missense NM_001407889.1:c.3976C>A NP_001394818.1:p.Gln1326Lys missense NM_001407894.1:c.3973C>A NP_001394823.1:p.Gln1325Lys missense NM_001407895.1:c.3973C>A NP_001394824.1:p.Gln1325Lys missense NM_001407896.1:c.3973C>A NP_001394825.1:p.Gln1325Lys missense NM_001407897.1:c.3973C>A NP_001394826.1:p.Gln1325Lys missense NM_001407898.1:c.3973C>A NP_001394827.1:p.Gln1325Lys missense NM_001407899.1:c.3973C>A NP_001394828.1:p.Gln1325Lys missense NM_001407900.1:c.3976C>A NP_001394829.1:p.Gln1326Lys missense NM_001407902.1:c.3976C>A NP_001394831.1:p.Gln1326Lys missense NM_001407904.1:c.3976C>A NP_001394833.1:p.Gln1326Lys missense NM_001407906.1:c.3976C>A NP_001394835.1:p.Gln1326Lys missense NM_001407916.1:c.3973C>A NP_001394845.1:p.Gln1325Lys missense NM_001407917.1:c.3973C>A NP_001394846.1:p.Gln1325Lys missense NM_001407918.1:c.3973C>A NP_001394847.1:p.Gln1325Lys missense NM_001407919.1:c.4063C>A NP_001394848.1:p.Gln1355Lys missense NM_001407920.1:c.3922C>A NP_001394849.1:p.Gln1308Lys missense NM_001407921.1:c.3922C>A NP_001394850.1:p.Gln1308Lys missense NM_001407922.1:c.3922C>A NP_001394851.1:p.Gln1308Lys missense NM_001407923.1:c.3922C>A NP_001394852.1:p.Gln1308Lys missense NM_001407924.1:c.3922C>A NP_001394853.1:p.Gln1308Lys missense NM_001407925.1:c.3922C>A NP_001394854.1:p.Gln1308Lys missense NM_001407926.1:c.3922C>A NP_001394855.1:p.Gln1308Lys missense NM_001407927.1:c.3922C>A NP_001394856.1:p.Gln1308Lys missense NM_001407928.1:c.3922C>A NP_001394857.1:p.Gln1308Lys missense NM_001407929.1:c.3922C>A NP_001394858.1:p.Gln1308Lys missense NM_001407930.1:c.3919C>A NP_001394859.1:p.Gln1307Lys missense NM_001407931.1:c.3919C>A NP_001394860.1:p.Gln1307Lys missense NM_001407932.1:c.3919C>A NP_001394861.1:p.Gln1307Lys missense NM_001407936.1:c.3919C>A NP_001394865.1:p.Gln1307Lys missense NM_001407937.1:c.4063C>A NP_001394866.1:p.Gln1355Lys missense NM_001407938.1:c.4063C>A NP_001394867.1:p.Gln1355Lys missense NM_001407939.1:c.4063C>A NP_001394868.1:p.Gln1355Lys missense NM_001407940.1:c.4060C>A NP_001394869.1:p.Gln1354Lys missense NM_001407941.1:c.4060C>A NP_001394870.1:p.Gln1354Lys missense NM_001407942.1:c.4045C>A NP_001394871.1:p.Gln1349Lys missense NM_001407943.1:c.4042C>A NP_001394872.1:p.Gln1348Lys missense NM_001407944.1:c.4045C>A NP_001394873.1:p.Gln1349Lys missense NM_001407945.1:c.4045C>A NP_001394874.1:p.Gln1349Lys missense NM_001407946.1:c.3853C>A NP_001394875.1:p.Gln1285Lys missense NM_001407947.1:c.3853C>A NP_001394876.1:p.Gln1285Lys missense NM_001407948.1:c.3853C>A NP_001394877.1:p.Gln1285Lys missense NM_001407949.1:c.3853C>A NP_001394878.1:p.Gln1285Lys missense NM_001407950.1:c.3853C>A NP_001394879.1:p.Gln1285Lys missense NM_001407951.1:c.3853C>A NP_001394880.1:p.Gln1285Lys missense NM_001407954.1:c.3850C>A NP_001394883.1:p.Gln1284Lys missense NM_001407955.1:c.3850C>A NP_001394884.1:p.Gln1284Lys missense NM_001407958.1:c.3850C>A NP_001394887.1:p.Gln1284Lys missense NM_001407959.1:c.3805C>A NP_001394888.1:p.Gln1269Lys missense NM_001407960.1:c.3805C>A NP_001394889.1:p.Gln1269Lys missense NM_001407962.1:c.3802C>A NP_001394891.1:p.Gln1268Lys missense NM_001407964.1:c.4042C>A NP_001394893.1:p.Gln1348Lys missense NM_001407966.1:c.3298C>A NP_001394895.1:p.Gln1100Lys missense NM_001407967.1:c.3298C>A NP_001394896.1:p.Gln1100Lys missense NM_001407968.1:c.1582C>A NP_001394897.1:p.Gln528Lys missense NM_001407970.1:c.877C>A NP_001394899.1:p.Gln293Lys missense NM_001407971.1:c.877C>A NP_001394900.1:p.Gln293Lys missense NM_001407972.1:c.874C>A NP_001394901.1:p.Gln292Lys missense NM_001407973.1:c.877C>A NP_001394902.1:p.Gln293Lys missense NM_001407974.1:c.877C>A NP_001394903.1:p.Gln293Lys missense NM_001407975.1:c.877C>A NP_001394904.1:p.Gln293Lys missense NM_001407976.1:c.877C>A NP_001394905.1:p.Gln293Lys missense NM_001407977.1:c.877C>A NP_001394906.1:p.Gln293Lys missense NM_001407978.1:c.877C>A NP_001394907.1:p.Gln293Lys missense NM_001407984.1:c.874C>A NP_001394913.1:p.Gln292Lys missense NM_001407985.1:c.874C>A NP_001394914.1:p.Gln292Lys missense NM_001407986.1:c.874C>A NP_001394915.1:p.Gln292Lys missense NM_001407991.1:c.874C>A NP_001394920.1:p.Gln292Lys missense NM_001407992.1:c.874C>A NP_001394921.1:p.Gln292Lys missense NM_001407993.1:c.877C>A NP_001394922.1:p.Gln293Lys missense NM_001408392.1:c.874C>A NP_001395321.1:p.Gln292Lys missense NM_001408396.1:c.874C>A NP_001395325.1:p.Gln292Lys missense NM_001408397.1:c.874C>A NP_001395326.1:p.Gln292Lys missense NM_001408398.1:c.874C>A NP_001395327.1:p.Gln292Lys missense NM_001408399.1:c.874C>A NP_001395328.1:p.Gln292Lys missense NM_001408408.1:c.868C>A NP_001395337.1:p.Gln290Lys missense NM_001408409.1:c.799C>A NP_001395338.1:p.Gln267Lys missense NM_001408410.1:c.736C>A NP_001395339.1:p.Gln246Lys missense NM_001408411.1:c.799C>A NP_001395340.1:p.Gln267Lys missense NM_001408412.1:c.799C>A NP_001395341.1:p.Gln267Lys missense NM_001408413.1:c.796C>A NP_001395342.1:p.Gln266Lys missense NM_001408414.1:c.799C>A NP_001395343.1:p.Gln267Lys missense NM_001408415.1:c.799C>A NP_001395344.1:p.Gln267Lys missense NM_001408416.1:c.796C>A NP_001395345.1:p.Gln266Lys missense NM_001408418.1:c.760C>A NP_001395347.1:p.Gln254Lys missense NM_001408419.1:c.760C>A NP_001395348.1:p.Gln254Lys missense NM_001408420.1:c.760C>A NP_001395349.1:p.Gln254Lys missense NM_001408421.1:c.757C>A NP_001395350.1:p.Gln253Lys missense NM_001408422.1:c.760C>A NP_001395351.1:p.Gln254Lys missense NM_001408423.1:c.760C>A NP_001395352.1:p.Gln254Lys missense NM_001408424.1:c.757C>A NP_001395353.1:p.Gln253Lys missense NM_001408425.1:c.754C>A NP_001395354.1:p.Gln252Lys missense NM_001408426.1:c.754C>A NP_001395355.1:p.Gln252Lys missense NM_001408427.1:c.754C>A NP_001395356.1:p.Gln252Lys missense NM_001408428.1:c.754C>A NP_001395357.1:p.Gln252Lys missense NM_001408429.1:c.754C>A NP_001395358.1:p.Gln252Lys missense NM_001408430.1:c.754C>A NP_001395359.1:p.Gln252Lys missense NM_001408431.1:c.757C>A NP_001395360.1:p.Gln253Lys missense NM_001408432.1:c.751C>A NP_001395361.1:p.Gln251Lys missense NM_001408433.1:c.751C>A NP_001395362.1:p.Gln251Lys missense NM_001408434.1:c.751C>A NP_001395363.1:p.Gln251Lys missense NM_001408435.1:c.751C>A NP_001395364.1:p.Gln251Lys missense NM_001408436.1:c.754C>A NP_001395365.1:p.Gln252Lys missense NM_001408437.1:c.754C>A NP_001395366.1:p.Gln252Lys missense NM_001408438.1:c.754C>A NP_001395367.1:p.Gln252Lys missense NM_001408439.1:c.754C>A NP_001395368.1:p.Gln252Lys missense NM_001408440.1:c.754C>A NP_001395369.1:p.Gln252Lys missense NM_001408445.1:c.751C>A NP_001395374.1:p.Gln251Lys missense NM_001408446.1:c.751C>A NP_001395375.1:p.Gln251Lys missense NM_001408447.1:c.751C>A NP_001395376.1:p.Gln251Lys missense NM_001408448.1:c.751C>A NP_001395377.1:p.Gln251Lys missense NM_001408450.1:c.751C>A NP_001395379.1:p.Gln251Lys missense NM_001408451.1:c.742C>A NP_001395380.1:p.Gln248Lys missense NM_001408452.1:c.736C>A NP_001395381.1:p.Gln246Lys missense NM_001408453.1:c.736C>A NP_001395382.1:p.Gln246Lys missense NM_001408454.1:c.736C>A NP_001395383.1:p.Gln246Lys missense NM_001408455.1:c.736C>A NP_001395384.1:p.Gln246Lys missense NM_001408456.1:c.736C>A NP_001395385.1:p.Gln246Lys missense NM_001408457.1:c.736C>A NP_001395386.1:p.Gln246Lys missense NM_001408458.1:c.736C>A NP_001395387.1:p.Gln246Lys missense NM_001408459.1:c.736C>A NP_001395388.1:p.Gln246Lys missense NM_001408460.1:c.736C>A NP_001395389.1:p.Gln246Lys missense NM_001408461.1:c.736C>A NP_001395390.1:p.Gln246Lys missense NM_001408462.1:c.733C>A NP_001395391.1:p.Gln245Lys missense NM_001408463.1:c.733C>A NP_001395392.1:p.Gln245Lys missense NM_001408464.1:c.733C>A NP_001395393.1:p.Gln245Lys missense NM_001408465.1:c.733C>A NP_001395394.1:p.Gln245Lys missense NM_001408468.1:c.733C>A NP_001395397.1:p.Gln245Lys missense NM_001408473.1:c.874C>A NP_001395402.1:p.Gln292Lys missense NM_001408474.1:c.676C>A NP_001395403.1:p.Gln226Lys missense NM_001408475.1:c.673C>A NP_001395404.1:p.Gln225Lys missense NM_001408476.1:c.676C>A NP_001395405.1:p.Gln226Lys missense NM_001408478.1:c.667C>A NP_001395407.1:p.Gln223Lys missense NM_001408479.1:c.667C>A NP_001395408.1:p.Gln223Lys missense NM_001408480.1:c.667C>A NP_001395409.1:p.Gln223Lys missense NM_001408481.1:c.667C>A NP_001395410.1:p.Gln223Lys missense NM_001408482.1:c.667C>A NP_001395411.1:p.Gln223Lys missense NM_001408483.1:c.667C>A NP_001395412.1:p.Gln223Lys missense NM_001408484.1:c.667C>A NP_001395413.1:p.Gln223Lys missense NM_001408485.1:c.667C>A NP_001395414.1:p.Gln223Lys missense NM_001408490.1:c.664C>A NP_001395419.1:p.Gln222Lys missense NM_001408491.1:c.664C>A NP_001395420.1:p.Gln222Lys missense NM_001408493.1:c.664C>A NP_001395422.1:p.Gln222Lys missense NM_001408494.1:c.637C>A NP_001395423.1:p.Gln213Lys missense NM_001408495.1:c.634C>A NP_001395424.1:p.Gln212Lys missense NM_001408496.1:c.613C>A NP_001395425.1:p.Gln205Lys missense NM_001408497.1:c.613C>A NP_001395426.1:p.Gln205Lys missense NM_001408498.1:c.613C>A NP_001395427.1:p.Gln205Lys missense NM_001408499.1:c.613C>A NP_001395428.1:p.Gln205Lys missense NM_001408500.1:c.613C>A NP_001395429.1:p.Gln205Lys missense NM_001408501.1:c.613C>A NP_001395430.1:p.Gln205Lys missense NM_001408502.1:c.544C>A NP_001395431.1:p.Gln182Lys missense NM_001408503.1:c.610C>A NP_001395432.1:p.Gln204Lys missense NM_001408504.1:c.610C>A NP_001395433.1:p.Gln204Lys missense NM_001408505.1:c.610C>A NP_001395434.1:p.Gln204Lys missense NM_001408506.1:c.550C>A NP_001395435.1:p.Gln184Lys missense NM_001408510.1:c.496C>A NP_001395439.1:p.Gln166Lys missense NM_001408511.1:c.493C>A NP_001395440.1:p.Gln165Lys missense NM_001408512.1:c.373C>A NP_001395441.1:p.Gln125Lys missense NM_001408514.1:c.667C>A NP_001395443.1:p.Gln223Lys missense NM_007297.4:c.4045C>A NP_009228.2:p.Gln1349Lys missense NM_007298.4:c.877C>A NP_009229.2:p.Gln293Lys missense NM_007299.4:c.877C>A NP_009230.2:p.Gln293Lys missense NM_007300.4:c.4186C>A NP_009231.2:p.Gln1396Lys missense NM_007304.2:c.877C>A NP_009235.2:p.Gln293Lys missense NR_027676.2:n.4363C>A non-coding transcript variant NC_000017.11:g.43082575G>T NC_000017.10:g.41234592G>T NG_005905.2:g.135409C>A LRG_292:g.135409C>A LRG_292t1:c.4186C>A LRG_292p1:p.Gln1396Lys - Protein change
- Q1396K, Q1349K, Q293K, Q1326K, Q1329K, Q246K, Q252K, Q266K, Q267K, Q292K, Q1100K, Q1269K, Q1285K, Q1348K, Q1370K, Q184K, Q205K, Q223K, Q225K, Q248K, Q251K, Q254K, Q290K, Q125K, Q1307K, Q1308K, Q1328K, Q1369K, Q165K, Q182K, Q212K, Q213K, Q226K, Q245K, Q253K, Q1268K, Q1284K, Q1325K, Q1354K, Q1355K, Q1395K, Q166K, Q204K, Q222K, Q528K
- Other names
-
p.Q1396K:CAG>AAG
- Canonical SPDI
- NC_000017.11:43082574:G:T
-
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.
-
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 |
13044 | 14850 | |
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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 12, 2018 | RCV000159988.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 27, 2023 | RCV000466202.11 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
May 26, 2023 | RCV001022002.5 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Oct 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000549259.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 1396 of the BRCA1 protein (p.Gln1396Lys). … (more)
This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 1396 of the BRCA1 protein (p.Gln1396Lys). This variant is present in population databases (rs80357011, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 182160). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. (less)
|
|
|
Uncertain significance
(May 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001183689.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The p.Q1396K variant (also known as c.4186C>A), located in coding exon 11 of the BRCA1 gene, results from a C to A substitution at nucleotide … (more)
The p.Q1396K variant (also known as c.4186C>A), located in coding exon 11 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4186. This variant impacts the first base pair of coding exon 11. The glutamine at codon 1396 is replaced by lysine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Kadri MSN et al. Front Oncol, 2020 Jan;10:568786). This amino acid position is highly 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. (less)
|
|
|
Uncertain significance
(Feb 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210171.13
First in ClinVar: Feb 24, 2015 Last updated: Jul 24, 2016 |
Comment:
This variant is denoted BRCA1 c.4186C>A at the cDNA level, p.Gln1396Lys (Q1396K) at the protein level, and results in the change of a Glutamine to … (more)
This variant is denoted BRCA1 c.4186C>A at the cDNA level, p.Gln1396Lys (Q1396K) at the protein level, and results in the change of a Glutamine to a Lysine (CAG>AAG). Using alternate nomenclature, this variant would be defined as BRCA1 4305C>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1396Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the SCD domain and in a region known to interact with multiple proteins (Chen 1998, Narod 2004, Clark 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Gln1396Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
|
Comment:
Comment:
The p.Q1396K variant (also known as c.4186C>A), located in coding exon 11 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4186. This variant impacts the first base pair of coding exon 11. The glutamine at codon 1396 is replaced by lysine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Kadri MSN et al. Front Oncol, 2020 Jan;10:568786). This amino acid position is highly 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.
Comment:
This variant is denoted BRCA1 c.4186C>A at the cDNA level, p.Gln1396Lys (Q1396K) at the protein level, and results in the change of a Glutamine to a Lysine (CAG>AAG). Using alternate nomenclature, this variant would be defined as BRCA1 4305C>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1396Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the SCD domain and in a region known to interact with multiple proteins (Chen 1998, Narod 2004, Clark 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Gln1396Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
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:
This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 1396 of the BRCA1 protein (p.Gln1396Lys). This variant is present in population databases (rs80357011, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 182160). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Comment:
The p.Q1396K variant (also known as c.4186C>A), located in coding exon 11 of the BRCA1 gene, results from a C to A substitution at nucleotide position 4186. This variant impacts the first base pair of coding exon 11. The glutamine at codon 1396 is replaced by lysine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Kadri MSN et al. Front Oncol, 2020 Jan;10:568786). This amino acid position is highly 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.
Comment:
This variant is denoted BRCA1 c.4186C>A at the cDNA level, p.Gln1396Lys (Q1396K) at the protein level, and results in the change of a Glutamine to a Lysine (CAG>AAG). Using alternate nomenclature, this variant would be defined as BRCA1 4305C>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Gln1396Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the SCD domain and in a region known to interact with multiple proteins (Chen 1998, Narod 2004, Clark 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BRCA1 Gln1396Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening. | Kadri MSN | Frontiers in oncology | 2021 | PMID: 33552952 |
Text-mined citations for rs80357011 ...
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.