This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1454 of the BRCA1 protein (p.Val1454Ile). This variant is not present in population databases (gnomAD no frequency). 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: 433712). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.4360G>A (p.Val1454Ile)
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.4360G>A (p.Val1454Ile)
Variation ID: 433712 Accession: VCV000433712.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43076612 (GRCh38) [ NCBI UCSC ] 17: 41228629 (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 Aug 28, 2017 Jan 13, 2025 Sep 10, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4360G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Val1454Ile missense NM_001407571.1:c.4147G>A NP_001394500.1:p.Val1383Ile missense NM_001407581.1:c.4426G>A NP_001394510.1:p.Val1476Ile missense NM_001407582.1:c.4426G>A NP_001394511.1:p.Val1476Ile missense NM_001407583.1:c.4424-1G>A splice acceptor NM_001407585.1:c.4424-1G>A splice acceptor NM_001407587.1:c.4423G>A NP_001394516.1:p.Val1475Ile missense NM_001407590.1:c.4421-1G>A splice acceptor NM_001407591.1:c.4421-1G>A splice acceptor NM_001407593.1:c.4360G>A NP_001394522.1:p.Val1454Ile missense NM_001407594.1:c.4360G>A NP_001394523.1:p.Val1454Ile missense NM_001407596.1:c.4360G>A NP_001394525.1:p.Val1454Ile missense NM_001407597.1:c.4360G>A NP_001394526.1:p.Val1454Ile missense NM_001407598.1:c.4360G>A NP_001394527.1:p.Val1454Ile missense NM_001407602.1:c.4360G>A NP_001394531.1:p.Val1454Ile missense NM_001407603.1:c.4360G>A NP_001394532.1:p.Val1454Ile missense NM_001407605.1:c.4360G>A NP_001394534.1:p.Val1454Ile missense NM_001407610.1:c.4357G>A NP_001394539.1:p.Val1453Ile missense NM_001407611.1:c.4357G>A NP_001394540.1:p.Val1453Ile missense NM_001407612.1:c.4357G>A NP_001394541.1:p.Val1453Ile missense NM_001407613.1:c.4357G>A NP_001394542.1:p.Val1453Ile missense NM_001407614.1:c.4357G>A NP_001394543.1:p.Val1453Ile missense NM_001407615.1:c.4357G>A NP_001394544.1:p.Val1453Ile missense NM_001407616.1:c.4358-1G>A splice acceptor NM_001407617.1:c.4358-1G>A splice acceptor NM_001407618.1:c.4358-1G>A splice acceptor NM_001407619.1:c.4358-1G>A splice acceptor NM_001407620.1:c.4358-1G>A splice acceptor NM_001407621.1:c.4358-1G>A splice acceptor NM_001407622.1:c.4358-1G>A splice acceptor NM_001407623.1:c.4358-1G>A splice acceptor NM_001407624.1:c.4357G>A NP_001394553.1:p.Val1453Ile missense NM_001407625.1:c.4357G>A NP_001394554.1:p.Val1453Ile missense NM_001407626.1:c.4357G>A NP_001394555.1:p.Val1453Ile missense NM_001407627.1:c.4354G>A NP_001394556.1:p.Val1452Ile missense NM_001407628.1:c.4354G>A NP_001394557.1:p.Val1452Ile missense NM_001407629.1:c.4354G>A NP_001394558.1:p.Val1452Ile missense NM_001407630.1:c.4354G>A NP_001394559.1:p.Val1452Ile missense NM_001407631.1:c.4354G>A NP_001394560.1:p.Val1452Ile missense NM_001407632.1:c.4354G>A NP_001394561.1:p.Val1452Ile missense NM_001407633.1:c.4355-1G>A splice acceptor NM_001407634.1:c.4355-1G>A splice acceptor NM_001407635.1:c.4355-1G>A splice acceptor NM_001407636.1:c.4355-1G>A splice acceptor NM_001407637.1:c.4355-1G>A splice acceptor NM_001407638.1:c.4355-1G>A splice acceptor NM_001407639.1:c.4355-1G>A splice acceptor NM_001407640.1:c.4355-1G>A splice acceptor NM_001407641.1:c.4355-1G>A splice acceptor NM_001407642.1:c.4355-1G>A splice acceptor NM_001407644.1:c.4352-1G>A splice acceptor NM_001407645.1:c.4352-1G>A splice acceptor NM_001407646.1:c.4348G>A NP_001394575.1:p.Val1450Ile missense NM_001407647.1:c.4346-1G>A splice acceptor NM_001407648.1:c.4303G>A NP_001394577.1:p.Val1435Ile missense NM_001407649.1:c.4300G>A NP_001394578.1:p.Val1434Ile missense NM_001407652.1:c.4360G>A NP_001394581.1:p.Val1454Ile missense NM_001407653.1:c.4282G>A NP_001394582.1:p.Val1428Ile missense NM_001407654.1:c.4282G>A NP_001394583.1:p.Val1428Ile missense NM_001407655.1:c.4282G>A NP_001394584.1:p.Val1428Ile missense NM_001407656.1:c.4279G>A NP_001394585.1:p.Val1427Ile missense NM_001407657.1:c.4280-1G>A splice acceptor NM_001407658.1:c.4280-1G>A splice acceptor NM_001407659.1:c.4276G>A NP_001394588.1:p.Val1426Ile missense NM_001407660.1:c.4276G>A NP_001394589.1:p.Val1426Ile missense NM_001407661.1:c.4277-1G>A splice acceptor NM_001407662.1:c.4277-1G>A splice acceptor NM_001407663.1:c.4277-1G>A splice acceptor NM_001407664.1:c.4237G>A NP_001394593.1:p.Val1413Ile missense NM_001407665.1:c.4237G>A NP_001394594.1:p.Val1413Ile missense NM_001407666.1:c.4237G>A NP_001394595.1:p.Val1413Ile missense NM_001407667.1:c.4237G>A NP_001394596.1:p.Val1413Ile missense NM_001407668.1:c.4237G>A NP_001394597.1:p.Val1413Ile missense NM_001407669.1:c.4237G>A NP_001394598.1:p.Val1413Ile missense NM_001407670.1:c.4234G>A NP_001394599.1:p.Val1412Ile missense NM_001407671.1:c.4234G>A NP_001394600.1:p.Val1412Ile missense NM_001407672.1:c.4234G>A NP_001394601.1:p.Val1412Ile missense NM_001407673.1:c.4234G>A NP_001394602.1:p.Val1412Ile missense NM_001407674.1:c.4234G>A NP_001394603.1:p.Val1412Ile missense NM_001407675.1:c.4234G>A NP_001394604.1:p.Val1412Ile missense NM_001407676.1:c.4234G>A NP_001394605.1:p.Val1412Ile missense NM_001407677.1:c.4235-1G>A splice acceptor NM_001407678.1:c.4235-1G>A splice acceptor NM_001407679.1:c.4235-1G>A splice acceptor NM_001407680.1:c.4235-1G>A splice acceptor NM_001407681.1:c.4232-1G>A splice acceptor NM_001407682.1:c.4232-1G>A splice acceptor NM_001407683.1:c.4232-1G>A splice acceptor NM_001407684.1:c.4360G>A NP_001394613.1:p.Val1454Ile missense NM_001407685.1:c.4231G>A NP_001394614.1:p.Val1411Ile missense NM_001407686.1:c.4231G>A NP_001394615.1:p.Val1411Ile missense NM_001407687.1:c.4231G>A NP_001394616.1:p.Val1411Ile missense NM_001407688.1:c.4232-1G>A splice acceptor NM_001407689.1:c.4232-1G>A splice acceptor NM_001407690.1:c.4229-1G>A splice acceptor NM_001407691.1:c.4229-1G>A splice acceptor NM_001407692.1:c.4219G>A NP_001394621.1:p.Val1407Ile missense NM_001407694.1:c.4219G>A NP_001394623.1:p.Val1407Ile missense NM_001407695.1:c.4219G>A NP_001394624.1:p.Val1407Ile missense NM_001407696.1:c.4219G>A NP_001394625.1:p.Val1407Ile missense NM_001407697.1:c.4219G>A NP_001394626.1:p.Val1407Ile missense NM_001407698.1:c.4219G>A NP_001394627.1:p.Val1407Ile missense NM_001407724.1:c.4219G>A NP_001394653.1:p.Val1407Ile missense NM_001407725.1:c.4219G>A NP_001394654.1:p.Val1407Ile missense NM_001407726.1:c.4219G>A NP_001394655.1:p.Val1407Ile missense NM_001407727.1:c.4219G>A NP_001394656.1:p.Val1407Ile missense NM_001407728.1:c.4219G>A NP_001394657.1:p.Val1407Ile missense NM_001407729.1:c.4219G>A NP_001394658.1:p.Val1407Ile missense NM_001407730.1:c.4219G>A NP_001394659.1:p.Val1407Ile missense NM_001407731.1:c.4219G>A NP_001394660.1:p.Val1407Ile missense NM_001407732.1:c.4217-1G>A splice acceptor NM_001407733.1:c.4217-1G>A splice acceptor NM_001407734.1:c.4217-1G>A splice acceptor NM_001407735.1:c.4217-1G>A splice acceptor NM_001407736.1:c.4217-1G>A splice acceptor NM_001407737.1:c.4217-1G>A splice acceptor NM_001407738.1:c.4217-1G>A splice acceptor NM_001407739.1:c.4217-1G>A splice acceptor NM_001407740.1:c.4216G>A NP_001394669.1:p.Val1406Ile missense NM_001407741.1:c.4216G>A NP_001394670.1:p.Val1406Ile missense NM_001407742.1:c.4216G>A NP_001394671.1:p.Val1406Ile missense NM_001407743.1:c.4216G>A NP_001394672.1:p.Val1406Ile missense NM_001407744.1:c.4216G>A NP_001394673.1:p.Val1406Ile missense NM_001407745.1:c.4216G>A NP_001394674.1:p.Val1406Ile missense NM_001407746.1:c.4216G>A NP_001394675.1:p.Val1406Ile missense NM_001407747.1:c.4216G>A NP_001394676.1:p.Val1406Ile missense NM_001407748.1:c.4216G>A NP_001394677.1:p.Val1406Ile missense NM_001407749.1:c.4216G>A NP_001394678.1:p.Val1406Ile missense NM_001407750.1:c.4216G>A NP_001394679.1:p.Val1406Ile missense NM_001407751.1:c.4216G>A NP_001394680.1:p.Val1406Ile missense NM_001407752.1:c.4216G>A NP_001394681.1:p.Val1406Ile missense NM_001407838.1:c.4214-1G>A splice acceptor NM_001407839.1:c.4214-1G>A splice acceptor NM_001407841.1:c.4214-1G>A splice acceptor NM_001407842.1:c.4214-1G>A splice acceptor NM_001407843.1:c.4214-1G>A splice acceptor NM_001407844.1:c.4214-1G>A splice acceptor NM_001407845.1:c.4214-1G>A splice acceptor NM_001407846.1:c.4214-1G>A splice acceptor NM_001407847.1:c.4213G>A NP_001394776.1:p.Val1405Ile missense NM_001407848.1:c.4213G>A NP_001394777.1:p.Val1405Ile missense NM_001407849.1:c.4213G>A NP_001394778.1:p.Val1405Ile missense NM_001407850.1:c.4214-1G>A splice acceptor NM_001407851.1:c.4214-1G>A splice acceptor NM_001407852.1:c.4214-1G>A splice acceptor NM_001407853.1:c.4213G>A NP_001394782.1:p.Val1405Ile missense NM_001407854.1:c.4360G>A NP_001394783.1:p.Val1454Ile missense NM_001407858.1:c.4358-1G>A splice acceptor NM_001407859.1:c.4358-1G>A splice acceptor NM_001407860.1:c.4357G>A NP_001394789.1:p.Val1453Ile missense NM_001407861.1:c.4355-1G>A splice acceptor NM_001407862.1:c.4159G>A NP_001394791.1:p.Val1387Ile missense NM_001407863.1:c.4235-1G>A splice acceptor NM_001407874.1:c.4154-1G>A splice acceptor NM_001407875.1:c.4154-1G>A splice acceptor NM_001407879.1:c.4150G>A NP_001394808.1:p.Val1384Ile missense NM_001407881.1:c.4150G>A NP_001394810.1:p.Val1384Ile missense NM_001407882.1:c.4150G>A NP_001394811.1:p.Val1384Ile missense NM_001407884.1:c.4150G>A NP_001394813.1:p.Val1384Ile missense NM_001407885.1:c.4150G>A NP_001394814.1:p.Val1384Ile missense NM_001407886.1:c.4150G>A NP_001394815.1:p.Val1384Ile missense NM_001407887.1:c.4150G>A NP_001394816.1:p.Val1384Ile missense NM_001407889.1:c.4150G>A NP_001394818.1:p.Val1384Ile missense NM_001407894.1:c.4147G>A NP_001394823.1:p.Val1383Ile missense NM_001407895.1:c.4147G>A NP_001394824.1:p.Val1383Ile missense NM_001407896.1:c.4147G>A NP_001394825.1:p.Val1383Ile missense NM_001407897.1:c.4147G>A NP_001394826.1:p.Val1383Ile missense NM_001407898.1:c.4147G>A NP_001394827.1:p.Val1383Ile missense NM_001407899.1:c.4147G>A NP_001394828.1:p.Val1383Ile missense NM_001407900.1:c.4148-1G>A splice acceptor NM_001407902.1:c.4148-1G>A splice acceptor NM_001407904.1:c.4148-1G>A splice acceptor NM_001407906.1:c.4148-1G>A splice acceptor NM_001407907.1:c.4147G>A NP_001394836.1:p.Val1383Ile missense NM_001407908.1:c.4147G>A NP_001394837.1:p.Val1383Ile missense NM_001407909.1:c.4147G>A NP_001394838.1:p.Val1383Ile missense NM_001407910.1:c.4147G>A NP_001394839.1:p.Val1383Ile missense NM_001407915.1:c.4144G>A NP_001394844.1:p.Val1382Ile missense NM_001407916.1:c.4145-1G>A splice acceptor NM_001407917.1:c.4145-1G>A splice acceptor NM_001407918.1:c.4145-1G>A splice acceptor NM_001407919.1:c.4237G>A NP_001394848.1:p.Val1413Ile missense NM_001407920.1:c.4096G>A NP_001394849.1:p.Val1366Ile missense NM_001407921.1:c.4096G>A NP_001394850.1:p.Val1366Ile missense NM_001407922.1:c.4096G>A NP_001394851.1:p.Val1366Ile missense NM_001407923.1:c.4096G>A NP_001394852.1:p.Val1366Ile missense NM_001407924.1:c.4096G>A NP_001394853.1:p.Val1366Ile missense NM_001407925.1:c.4096G>A NP_001394854.1:p.Val1366Ile missense NM_001407926.1:c.4096G>A NP_001394855.1:p.Val1366Ile missense NM_001407927.1:c.4094-1G>A splice acceptor NM_001407928.1:c.4094-1G>A splice acceptor NM_001407929.1:c.4094-1G>A splice acceptor NM_001407930.1:c.4093G>A NP_001394859.1:p.Val1365Ile missense NM_001407931.1:c.4093G>A NP_001394860.1:p.Val1365Ile missense NM_001407932.1:c.4093G>A NP_001394861.1:p.Val1365Ile missense NM_001407933.1:c.4093G>A NP_001394862.1:p.Val1365Ile missense NM_001407934.1:c.4090G>A NP_001394863.1:p.Val1364Ile missense NM_001407935.1:c.4091-1G>A splice acceptor NM_001407936.1:c.4091-1G>A splice acceptor NM_001407937.1:c.4237G>A NP_001394866.1:p.Val1413Ile missense NM_001407938.1:c.4237G>A NP_001394867.1:p.Val1413Ile missense NM_001407939.1:c.4235-1G>A splice acceptor NM_001407940.1:c.4234G>A NP_001394869.1:p.Val1412Ile missense NM_001407941.1:c.4232-1G>A splice acceptor NM_001407942.1:c.4219G>A NP_001394871.1:p.Val1407Ile missense NM_001407943.1:c.4216G>A NP_001394872.1:p.Val1406Ile missense NM_001407944.1:c.4217-1G>A splice acceptor NM_001407945.1:c.4217-1G>A splice acceptor NM_001407946.1:c.4027G>A NP_001394875.1:p.Val1343Ile missense NM_001407947.1:c.4027G>A NP_001394876.1:p.Val1343Ile missense NM_001407948.1:c.4027G>A NP_001394877.1:p.Val1343Ile missense NM_001407949.1:c.4027G>A NP_001394878.1:p.Val1343Ile missense NM_001407950.1:c.4025-1G>A splice acceptor NM_001407951.1:c.4025-1G>A splice acceptor NM_001407952.1:c.4024G>A NP_001394881.1:p.Val1342Ile missense NM_001407953.1:c.4024G>A NP_001394882.1:p.Val1342Ile missense NM_001407954.1:c.4024G>A NP_001394883.1:p.Val1342Ile missense NM_001407955.1:c.4024G>A NP_001394884.1:p.Val1342Ile missense NM_001407956.1:c.4021G>A NP_001394885.1:p.Val1341Ile missense NM_001407957.1:c.4022-1G>A splice acceptor NM_001407958.1:c.4022-1G>A splice acceptor NM_001407959.1:c.3979G>A NP_001394888.1:p.Val1327Ile missense NM_001407960.1:c.3977-1G>A splice acceptor NM_001407962.1:c.3976G>A NP_001394891.1:p.Val1326Ile missense NM_001407963.1:c.3974-1G>A splice acceptor NM_001407964.1:c.4214-5374G>A intron variant NM_001407965.1:c.3853G>A NP_001394894.1:p.Val1285Ile missense NM_001407966.1:c.3472G>A NP_001394895.1:p.Val1158Ile missense NM_001407967.1:c.3470-1G>A splice acceptor NM_001407968.1:c.1756G>A NP_001394897.1:p.Val586Ile missense NM_001407969.1:c.1753G>A NP_001394898.1:p.Val585Ile missense NM_001407970.1:c.1117G>A NP_001394899.1:p.Val373Ile missense NM_001407971.1:c.1117G>A NP_001394900.1:p.Val373Ile missense NM_001407972.1:c.1114G>A NP_001394901.1:p.Val372Ile missense NM_001407973.1:c.1051G>A NP_001394902.1:p.Val351Ile missense NM_001407974.1:c.1051G>A NP_001394903.1:p.Val351Ile missense NM_001407975.1:c.1051G>A NP_001394904.1:p.Val351Ile missense NM_001407976.1:c.1051G>A NP_001394905.1:p.Val351Ile missense NM_001407977.1:c.1051G>A NP_001394906.1:p.Val351Ile missense NM_001407978.1:c.1051G>A NP_001394907.1:p.Val351Ile missense NM_001407979.1:c.1048G>A NP_001394908.1:p.Val350Ile missense NM_001407980.1:c.1048G>A NP_001394909.1:p.Val350Ile missense NM_001407981.1:c.1048G>A NP_001394910.1:p.Val350Ile missense NM_001407982.1:c.1048G>A NP_001394911.1:p.Val350Ile missense NM_001407983.1:c.1048G>A NP_001394912.1:p.Val350Ile missense NM_001407984.1:c.1048G>A NP_001394913.1:p.Val350Ile missense NM_001407985.1:c.1048G>A NP_001394914.1:p.Val350Ile missense NM_001407986.1:c.1048G>A NP_001394915.1:p.Val350Ile missense NM_001407990.1:c.1048G>A NP_001394919.1:p.Val350Ile missense NM_001407991.1:c.1048G>A NP_001394920.1:p.Val350Ile missense NM_001407992.1:c.1048G>A NP_001394921.1:p.Val350Ile missense NM_001407993.1:c.1049-1G>A splice acceptor NM_001408392.1:c.1046-1G>A splice acceptor NM_001408396.1:c.1046-1G>A splice acceptor NM_001408397.1:c.1046-1G>A splice acceptor NM_001408398.1:c.1046-1G>A splice acceptor NM_001408399.1:c.1046-1G>A splice acceptor NM_001408400.1:c.1045G>A NP_001395329.1:p.Val349Ile missense NM_001408401.1:c.1045G>A NP_001395330.1:p.Val349Ile missense NM_001408402.1:c.1045G>A NP_001395331.1:p.Val349Ile missense NM_001408403.1:c.1046-1G>A splice acceptor NM_001408404.1:c.1046-1G>A splice acceptor NM_001408406.1:c.1042G>A NP_001395335.1:p.Val348Ile missense NM_001408407.1:c.1043-1G>A splice acceptor NM_001408408.1:c.1042G>A NP_001395337.1:p.Val348Ile missense NM_001408409.1:c.1039G>A NP_001395338.1:p.Val347Ile missense NM_001408410.1:c.976G>A NP_001395339.1:p.Val326Ile missense NM_001408411.1:c.973G>A NP_001395340.1:p.Val325Ile missense NM_001408412.1:c.971-1G>A splice acceptor NM_001408413.1:c.970G>A NP_001395342.1:p.Val324Ile missense NM_001408414.1:c.971-1G>A splice acceptor NM_001408415.1:c.971-1G>A splice acceptor NM_001408416.1:c.970G>A NP_001395345.1:p.Val324Ile missense NM_001408418.1:c.934G>A NP_001395347.1:p.Val312Ile missense NM_001408419.1:c.934G>A NP_001395348.1:p.Val312Ile missense NM_001408420.1:c.934G>A NP_001395349.1:p.Val312Ile missense NM_001408421.1:c.931G>A NP_001395350.1:p.Val311Ile missense NM_001408422.1:c.932-1G>A splice acceptor NM_001408423.1:c.932-1G>A splice acceptor NM_001408424.1:c.931G>A NP_001395353.1:p.Val311Ile missense NM_001408425.1:c.928G>A NP_001395354.1:p.Val310Ile missense NM_001408426.1:c.928G>A NP_001395355.1:p.Val310Ile missense NM_001408427.1:c.928G>A NP_001395356.1:p.Val310Ile missense NM_001408428.1:c.928G>A NP_001395357.1:p.Val310Ile missense NM_001408429.1:c.928G>A NP_001395358.1:p.Val310Ile missense NM_001408430.1:c.928G>A NP_001395359.1:p.Val310Ile missense NM_001408431.1:c.929-1G>A splice acceptor NM_001408432.1:c.925G>A NP_001395361.1:p.Val309Ile missense NM_001408433.1:c.925G>A NP_001395362.1:p.Val309Ile missense NM_001408434.1:c.925G>A NP_001395363.1:p.Val309Ile missense NM_001408435.1:c.925G>A NP_001395364.1:p.Val309Ile missense NM_001408436.1:c.926-1G>A splice acceptor NM_001408437.1:c.926-1G>A splice acceptor NM_001408438.1:c.926-1G>A splice acceptor NM_001408439.1:c.926-1G>A splice acceptor NM_001408440.1:c.926-1G>A splice acceptor NM_001408441.1:c.925G>A NP_001395370.1:p.Val309Ile missense NM_001408442.1:c.925G>A NP_001395371.1:p.Val309Ile missense NM_001408443.1:c.925G>A NP_001395372.1:p.Val309Ile missense NM_001408444.1:c.925G>A NP_001395373.1:p.Val309Ile missense NM_001408445.1:c.923-1G>A splice acceptor NM_001408446.1:c.923-1G>A splice acceptor NM_001408447.1:c.923-1G>A splice acceptor NM_001408448.1:c.923-1G>A splice acceptor NM_001408450.1:c.923-1G>A splice acceptor NM_001408451.1:c.916G>A NP_001395380.1:p.Val306Ile missense NM_001408452.1:c.910G>A NP_001395381.1:p.Val304Ile missense NM_001408453.1:c.910G>A NP_001395382.1:p.Val304Ile missense NM_001408454.1:c.910G>A NP_001395383.1:p.Val304Ile missense NM_001408455.1:c.910G>A NP_001395384.1:p.Val304Ile missense NM_001408456.1:c.910G>A NP_001395385.1:p.Val304Ile missense NM_001408457.1:c.910G>A NP_001395386.1:p.Val304Ile missense NM_001408458.1:c.908-1G>A splice acceptor NM_001408459.1:c.908-1G>A splice acceptor NM_001408460.1:c.908-1G>A splice acceptor NM_001408461.1:c.908-1G>A splice acceptor NM_001408462.1:c.907G>A NP_001395391.1:p.Val303Ile missense NM_001408463.1:c.907G>A NP_001395392.1:p.Val303Ile missense NM_001408464.1:c.907G>A NP_001395393.1:p.Val303Ile missense NM_001408465.1:c.907G>A NP_001395394.1:p.Val303Ile missense NM_001408466.1:c.907G>A NP_001395395.1:p.Val303Ile missense NM_001408467.1:c.907G>A NP_001395396.1:p.Val303Ile missense NM_001408468.1:c.905-1G>A splice acceptor NM_001408469.1:c.905-1G>A splice acceptor NM_001408470.1:c.904G>A NP_001395399.1:p.Val302Ile missense NM_001408472.1:c.1048G>A NP_001395401.1:p.Val350Ile missense NM_001408473.1:c.1046-1G>A splice acceptor NM_001408474.1:c.850G>A NP_001395403.1:p.Val284Ile missense NM_001408475.1:c.847G>A NP_001395404.1:p.Val283Ile missense NM_001408476.1:c.848-1G>A splice acceptor NM_001408478.1:c.841G>A NP_001395407.1:p.Val281Ile missense NM_001408479.1:c.841G>A NP_001395408.1:p.Val281Ile missense NM_001408480.1:c.841G>A NP_001395409.1:p.Val281Ile missense NM_001408481.1:c.839-1G>A splice acceptor NM_001408482.1:c.839-1G>A splice acceptor NM_001408483.1:c.839-1G>A splice acceptor NM_001408484.1:c.839-1G>A splice acceptor NM_001408485.1:c.839-1G>A splice acceptor NM_001408489.1:c.838G>A NP_001395418.1:p.Val280Ile missense NM_001408490.1:c.838G>A NP_001395419.1:p.Val280Ile missense NM_001408491.1:c.838G>A NP_001395420.1:p.Val280Ile missense NM_001408492.1:c.836-1G>A splice acceptor NM_001408493.1:c.836-1G>A splice acceptor NM_001408494.1:c.811G>A NP_001395423.1:p.Val271Ile missense NM_001408495.1:c.806-1G>A splice acceptor NM_001408496.1:c.787G>A NP_001395425.1:p.Val263Ile missense NM_001408497.1:c.787G>A NP_001395426.1:p.Val263Ile missense NM_001408498.1:c.787G>A NP_001395427.1:p.Val263Ile missense NM_001408499.1:c.787G>A NP_001395428.1:p.Val263Ile missense NM_001408500.1:c.787G>A NP_001395429.1:p.Val263Ile missense NM_001408501.1:c.787G>A NP_001395430.1:p.Val263Ile missense NM_001408502.1:c.784G>A NP_001395431.1:p.Val262Ile missense NM_001408503.1:c.784G>A NP_001395432.1:p.Val262Ile missense NM_001408504.1:c.784G>A NP_001395433.1:p.Val262Ile missense NM_001408505.1:c.782-1G>A splice acceptor NM_001408506.1:c.724G>A NP_001395435.1:p.Val242Ile missense NM_001408507.1:c.721G>A NP_001395436.1:p.Val241Ile missense NM_001408508.1:c.712G>A NP_001395437.1:p.Val238Ile missense NM_001408509.1:c.710-1G>A splice acceptor NM_001408510.1:c.670G>A NP_001395439.1:p.Val224Ile missense NM_001408511.1:c.667G>A NP_001395440.1:p.Val223Ile missense NM_001408512.1:c.547G>A NP_001395441.1:p.Val183Ile missense NM_001408513.1:c.836-5374G>A intron variant NM_001408514.1:c.838+5792G>A intron variant NM_007297.4:c.4219G>A NP_009228.2:p.Val1407Ile missense NM_007298.4:c.1049-1G>A splice acceptor NM_007299.4:c.1049-1G>A splice acceptor NM_007300.4:c.4424-1G>A splice acceptor NR_027676.2:n.4537G>A NC_000017.11:g.43076612C>T NC_000017.10:g.41228629C>T NG_005905.2:g.141372G>A LRG_292:g.141372G>A LRG_292t1:c.4360G>A LRG_292p1:p.Val1454Ile - Protein change
- V1454I, V1407I, V1364I, V1383I, V1405I, V1406I, V1426I, V1427I, V1428I, V1435I, V1475I, V223I, V238I, V271I, V304I, V309I, V310I, V324I, V349I, V372I, V373I, V585I, V586I, V1158I, V1285I, V1342I, V1365I, V1382I, V1387I, V1412I, V1452I, V1453I, V1476I, V224I, V262I, V263I, V302I, V303I, V306I, V311I, V312I, V326I, V351I, V1326I, V1341I, V1343I, V1434I, V1450I, V281I, V348I, V1327I, V1366I, V1384I, V1411I, V1413I, V183I, V241I, V242I, V280I, V283I, V284I, V325I, V347I, V350I
- Other names
- -
- Canonical SPDI
- NC_000017.11:43076611:C: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.
- -
- 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 |
13146 | 14976 | |
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) |
no assertion criteria provided
|
- | RCV000501000.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 13, 2023 | RCV001037456.10 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 10, 2024 | RCV002329188.3 |
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 13, 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: SCV001200870.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1454 of the BRCA1 protein (p.Val1454Ile). … (more)
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1454 of the BRCA1 protein (p.Val1454Ile). This variant is not present in population databases (gnomAD no frequency). 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: 433712). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
(Sep 10, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002632945.3
First in ClinVar: Nov 29, 2022 Last updated: Jan 13, 2025 |
Comment:
The p.V1454I variant (also known as c.4360G>A), located in coding exon 12 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.V1454I variant (also known as c.4360G>A), located in coding exon 12 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4360. The valine at codon 1454 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. (less)
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591512.2 First in ClinVar: Aug 28, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Val1454Ile variant was not identified in the literature nor was it identified in the Exome Variant Server, HGMD, UMD, COSMIC, LOVD or BIC databases. … (more)
The p.Val1454Ile variant was not identified in the literature nor was it identified in the Exome Variant Server, HGMD, UMD, COSMIC, LOVD or BIC databases. The Val1454 residue is not conserved in mammals and the variant amino acid Isoleucine (Ile) is present in mouse and cow, increasing the likelihood this variant does not have clinical significance. Computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, the variant occurs 3bp away from the 5' splice site but it is not predicted to alter splicing, although the possibility that this variant could affect splicing cannot be ruled out. In summary, based on the above information, the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown significance. (less)
|
Comment:
Comment:
The p.V1454I variant (also known as c.4360G>A), located in coding exon 12 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4360. The valine at codon 1454 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Comment:
The p.Val1454Ile variant was not identified in the literature nor was it identified in the Exome Variant Server, HGMD, UMD, COSMIC, LOVD or BIC databases. The Val1454 residue is not conserved in mammals and the variant amino acid Isoleucine (Ile) is present in mouse and cow, increasing the likelihood this variant does not have clinical significance. Computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, the variant occurs 3bp away from the 5' splice site but it is not predicted to alter splicing, although the possibility that this variant could affect splicing cannot be ruled out. In summary, based on the above information, the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown 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 valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1454 of the BRCA1 protein (p.Val1454Ile). This variant is not present in population databases (gnomAD no frequency). 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: 433712). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.V1454I variant (also known as c.4360G>A), located in coding exon 12 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4360. The valine at codon 1454 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and isoleucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Comment:
The p.Val1454Ile variant was not identified in the literature nor was it identified in the Exome Variant Server, HGMD, UMD, COSMIC, LOVD or BIC databases. The Val1454 residue is not conserved in mammals and the variant amino acid Isoleucine (Ile) is present in mouse and cow, increasing the likelihood this variant does not have clinical significance. Computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. In addition, the variant occurs 3bp away from the 5' splice site but it is not predicted to alter splicing, although the possibility that this variant could affect splicing cannot be ruled out. In summary, based on the above information, the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown significance.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1555582714 ...
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 Jan 13, 2025
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.