This variant is denoted BRCA1 c.4055A>T at the cDNA level, p.Glu1352Val (E1352V) at the protein level, and results in the change of a Glutamic Acid to a Valine (GAA>GTA). Using alternate nomenclature, this variant would be defined as BRCA1 4174A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu1352Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1352Val occurs at a position that is not conserved and is located in the SCD domain as well as a region known to interact with multiple proteins (Narod 2004, Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Glu1352Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4055A>T (p.Glu1352Val)
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.
(8)
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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.
Conflicting classifications of pathogenicity
Uncertain significance(6); Likely benign(2)
Uncertain significance(6); Likely benign(2)
8
criteria provided, conflicting classifications
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.4055A>T (p.Glu1352Val)
Variation ID: 246375 Accession: VCV000246375.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43091476 (GRCh38) [ NCBI UCSC ] 17: 41243493 (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 25, 2016 Oct 20, 2024 Mar 8, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4055A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Glu1352Val missense NM_001407571.1:c.3842A>T NP_001394500.1:p.Glu1281Val missense NM_001407581.1:c.4055A>T NP_001394510.1:p.Glu1352Val missense NM_001407582.1:c.4055A>T NP_001394511.1:p.Glu1352Val missense NM_001407583.1:c.4055A>T NP_001394512.1:p.Glu1352Val missense NM_001407585.1:c.4055A>T NP_001394514.1:p.Glu1352Val missense NM_001407587.1:c.4052A>T NP_001394516.1:p.Glu1351Val missense NM_001407590.1:c.4052A>T NP_001394519.1:p.Glu1351Val missense NM_001407591.1:c.4052A>T NP_001394520.1:p.Glu1351Val missense NM_001407593.1:c.4055A>T NP_001394522.1:p.Glu1352Val missense NM_001407594.1:c.4055A>T NP_001394523.1:p.Glu1352Val missense NM_001407596.1:c.4055A>T NP_001394525.1:p.Glu1352Val missense NM_001407597.1:c.4055A>T NP_001394526.1:p.Glu1352Val missense NM_001407598.1:c.4055A>T NP_001394527.1:p.Glu1352Val missense NM_001407602.1:c.4055A>T NP_001394531.1:p.Glu1352Val missense NM_001407603.1:c.4055A>T NP_001394532.1:p.Glu1352Val missense NM_001407605.1:c.4055A>T NP_001394534.1:p.Glu1352Val missense NM_001407610.1:c.4052A>T NP_001394539.1:p.Glu1351Val missense NM_001407611.1:c.4052A>T NP_001394540.1:p.Glu1351Val missense NM_001407612.1:c.4052A>T NP_001394541.1:p.Glu1351Val missense NM_001407613.1:c.4052A>T NP_001394542.1:p.Glu1351Val missense NM_001407614.1:c.4052A>T NP_001394543.1:p.Glu1351Val missense NM_001407615.1:c.4052A>T NP_001394544.1:p.Glu1351Val missense NM_001407616.1:c.4055A>T NP_001394545.1:p.Glu1352Val missense NM_001407617.1:c.4055A>T NP_001394546.1:p.Glu1352Val missense NM_001407618.1:c.4055A>T NP_001394547.1:p.Glu1352Val missense NM_001407619.1:c.4055A>T NP_001394548.1:p.Glu1352Val missense NM_001407620.1:c.4055A>T NP_001394549.1:p.Glu1352Val missense NM_001407621.1:c.4055A>T NP_001394550.1:p.Glu1352Val missense NM_001407622.1:c.4055A>T NP_001394551.1:p.Glu1352Val missense NM_001407623.1:c.4055A>T NP_001394552.1:p.Glu1352Val missense NM_001407624.1:c.4055A>T NP_001394553.1:p.Glu1352Val missense NM_001407625.1:c.4055A>T NP_001394554.1:p.Glu1352Val missense NM_001407626.1:c.4055A>T NP_001394555.1:p.Glu1352Val missense NM_001407627.1:c.4052A>T NP_001394556.1:p.Glu1351Val missense NM_001407628.1:c.4052A>T NP_001394557.1:p.Glu1351Val missense NM_001407629.1:c.4052A>T NP_001394558.1:p.Glu1351Val missense NM_001407630.1:c.4052A>T NP_001394559.1:p.Glu1351Val missense NM_001407631.1:c.4052A>T NP_001394560.1:p.Glu1351Val missense NM_001407632.1:c.4052A>T NP_001394561.1:p.Glu1351Val missense NM_001407633.1:c.4052A>T NP_001394562.1:p.Glu1351Val missense NM_001407634.1:c.4052A>T NP_001394563.1:p.Glu1351Val missense NM_001407635.1:c.4052A>T NP_001394564.1:p.Glu1351Val missense NM_001407636.1:c.4052A>T NP_001394565.1:p.Glu1351Val missense NM_001407637.1:c.4052A>T NP_001394566.1:p.Glu1351Val missense NM_001407638.1:c.4052A>T NP_001394567.1:p.Glu1351Val missense NM_001407639.1:c.4055A>T NP_001394568.1:p.Glu1352Val missense NM_001407640.1:c.4055A>T NP_001394569.1:p.Glu1352Val missense NM_001407641.1:c.4055A>T NP_001394570.1:p.Glu1352Val missense NM_001407642.1:c.4055A>T NP_001394571.1:p.Glu1352Val missense NM_001407644.1:c.4052A>T NP_001394573.1:p.Glu1351Val missense NM_001407645.1:c.4052A>T NP_001394574.1:p.Glu1351Val missense NM_001407646.1:c.4046A>T NP_001394575.1:p.Glu1349Val missense NM_001407647.1:c.4046A>T NP_001394576.1:p.Glu1349Val missense NM_001407648.1:c.3932A>T NP_001394577.1:p.Glu1311Val missense NM_001407649.1:c.3929A>T NP_001394578.1:p.Glu1310Val missense NM_001407652.1:c.4055A>T NP_001394581.1:p.Glu1352Val missense NM_001407653.1:c.3977A>T NP_001394582.1:p.Glu1326Val missense NM_001407654.1:c.3977A>T NP_001394583.1:p.Glu1326Val missense NM_001407655.1:c.3977A>T NP_001394584.1:p.Glu1326Val missense NM_001407656.1:c.3977A>T NP_001394585.1:p.Glu1326Val missense NM_001407657.1:c.3977A>T NP_001394586.1:p.Glu1326Val missense NM_001407658.1:c.3977A>T NP_001394587.1:p.Glu1326Val missense NM_001407659.1:c.3974A>T NP_001394588.1:p.Glu1325Val missense NM_001407660.1:c.3974A>T NP_001394589.1:p.Glu1325Val missense NM_001407661.1:c.3974A>T NP_001394590.1:p.Glu1325Val missense NM_001407662.1:c.3974A>T NP_001394591.1:p.Glu1325Val missense NM_001407663.1:c.3977A>T NP_001394592.1:p.Glu1326Val missense NM_001407664.1:c.3932A>T NP_001394593.1:p.Glu1311Val missense NM_001407665.1:c.3932A>T NP_001394594.1:p.Glu1311Val missense NM_001407666.1:c.3932A>T NP_001394595.1:p.Glu1311Val missense NM_001407667.1:c.3932A>T NP_001394596.1:p.Glu1311Val missense NM_001407668.1:c.3932A>T NP_001394597.1:p.Glu1311Val missense NM_001407669.1:c.3932A>T NP_001394598.1:p.Glu1311Val missense NM_001407670.1:c.3929A>T NP_001394599.1:p.Glu1310Val missense NM_001407671.1:c.3929A>T NP_001394600.1:p.Glu1310Val missense NM_001407672.1:c.3929A>T NP_001394601.1:p.Glu1310Val missense NM_001407673.1:c.3929A>T NP_001394602.1:p.Glu1310Val missense NM_001407674.1:c.3932A>T NP_001394603.1:p.Glu1311Val missense NM_001407675.1:c.3932A>T NP_001394604.1:p.Glu1311Val missense NM_001407676.1:c.3932A>T NP_001394605.1:p.Glu1311Val missense NM_001407677.1:c.3932A>T NP_001394606.1:p.Glu1311Val missense NM_001407678.1:c.3932A>T NP_001394607.1:p.Glu1311Val missense NM_001407679.1:c.3932A>T NP_001394608.1:p.Glu1311Val missense NM_001407680.1:c.3932A>T NP_001394609.1:p.Glu1311Val missense NM_001407681.1:c.3932A>T NP_001394610.1:p.Glu1311Val missense NM_001407682.1:c.3932A>T NP_001394611.1:p.Glu1311Val missense NM_001407683.1:c.3932A>T NP_001394612.1:p.Glu1311Val missense NM_001407684.1:c.4055A>T NP_001394613.1:p.Glu1352Val missense NM_001407685.1:c.3929A>T NP_001394614.1:p.Glu1310Val missense NM_001407686.1:c.3929A>T NP_001394615.1:p.Glu1310Val missense NM_001407687.1:c.3929A>T NP_001394616.1:p.Glu1310Val missense NM_001407688.1:c.3929A>T NP_001394617.1:p.Glu1310Val missense NM_001407689.1:c.3929A>T NP_001394618.1:p.Glu1310Val missense NM_001407690.1:c.3929A>T NP_001394619.1:p.Glu1310Val missense NM_001407691.1:c.3929A>T NP_001394620.1:p.Glu1310Val missense NM_001407692.1:c.3914A>T NP_001394621.1:p.Glu1305Val missense NM_001407694.1:c.3914A>T NP_001394623.1:p.Glu1305Val missense NM_001407695.1:c.3914A>T NP_001394624.1:p.Glu1305Val missense NM_001407696.1:c.3914A>T NP_001394625.1:p.Glu1305Val missense NM_001407697.1:c.3914A>T NP_001394626.1:p.Glu1305Val missense NM_001407698.1:c.3914A>T NP_001394627.1:p.Glu1305Val missense NM_001407724.1:c.3914A>T NP_001394653.1:p.Glu1305Val missense NM_001407725.1:c.3914A>T NP_001394654.1:p.Glu1305Val missense NM_001407726.1:c.3914A>T NP_001394655.1:p.Glu1305Val missense NM_001407727.1:c.3914A>T NP_001394656.1:p.Glu1305Val missense NM_001407728.1:c.3914A>T NP_001394657.1:p.Glu1305Val missense NM_001407729.1:c.3914A>T NP_001394658.1:p.Glu1305Val missense NM_001407730.1:c.3914A>T NP_001394659.1:p.Glu1305Val missense NM_001407731.1:c.3914A>T NP_001394660.1:p.Glu1305Val missense NM_001407732.1:c.3914A>T NP_001394661.1:p.Glu1305Val missense NM_001407733.1:c.3914A>T NP_001394662.1:p.Glu1305Val missense NM_001407734.1:c.3914A>T NP_001394663.1:p.Glu1305Val missense NM_001407735.1:c.3914A>T NP_001394664.1:p.Glu1305Val missense NM_001407736.1:c.3914A>T NP_001394665.1:p.Glu1305Val missense NM_001407737.1:c.3914A>T NP_001394666.1:p.Glu1305Val missense NM_001407738.1:c.3914A>T NP_001394667.1:p.Glu1305Val missense NM_001407739.1:c.3914A>T NP_001394668.1:p.Glu1305Val missense NM_001407740.1:c.3911A>T NP_001394669.1:p.Glu1304Val missense NM_001407741.1:c.3911A>T NP_001394670.1:p.Glu1304Val missense NM_001407742.1:c.3911A>T NP_001394671.1:p.Glu1304Val missense NM_001407743.1:c.3911A>T NP_001394672.1:p.Glu1304Val missense NM_001407744.1:c.3911A>T NP_001394673.1:p.Glu1304Val missense NM_001407745.1:c.3911A>T NP_001394674.1:p.Glu1304Val missense NM_001407746.1:c.3911A>T NP_001394675.1:p.Glu1304Val missense NM_001407747.1:c.3911A>T NP_001394676.1:p.Glu1304Val missense NM_001407748.1:c.3911A>T NP_001394677.1:p.Glu1304Val missense NM_001407749.1:c.3911A>T NP_001394678.1:p.Glu1304Val missense NM_001407750.1:c.3914A>T NP_001394679.1:p.Glu1305Val missense NM_001407751.1:c.3914A>T NP_001394680.1:p.Glu1305Val missense NM_001407752.1:c.3914A>T NP_001394681.1:p.Glu1305Val missense NM_001407838.1:c.3911A>T NP_001394767.1:p.Glu1304Val missense NM_001407839.1:c.3911A>T NP_001394768.1:p.Glu1304Val missense NM_001407841.1:c.3911A>T NP_001394770.1:p.Glu1304Val missense NM_001407842.1:c.3911A>T NP_001394771.1:p.Glu1304Val missense NM_001407843.1:c.3911A>T NP_001394772.1:p.Glu1304Val missense NM_001407844.1:c.3911A>T NP_001394773.1:p.Glu1304Val missense NM_001407845.1:c.3911A>T NP_001394774.1:p.Glu1304Val missense NM_001407846.1:c.3911A>T NP_001394775.1:p.Glu1304Val missense NM_001407847.1:c.3911A>T NP_001394776.1:p.Glu1304Val missense NM_001407848.1:c.3911A>T NP_001394777.1:p.Glu1304Val missense NM_001407849.1:c.3911A>T NP_001394778.1:p.Glu1304Val missense NM_001407850.1:c.3914A>T NP_001394779.1:p.Glu1305Val missense NM_001407851.1:c.3914A>T NP_001394780.1:p.Glu1305Val missense NM_001407852.1:c.3914A>T NP_001394781.1:p.Glu1305Val missense NM_001407853.1:c.3842A>T NP_001394782.1:p.Glu1281Val missense NM_001407854.1:c.4055A>T NP_001394783.1:p.Glu1352Val missense NM_001407858.1:c.4055A>T NP_001394787.1:p.Glu1352Val missense NM_001407859.1:c.4055A>T NP_001394788.1:p.Glu1352Val missense NM_001407860.1:c.4052A>T NP_001394789.1:p.Glu1351Val missense NM_001407861.1:c.4052A>T NP_001394790.1:p.Glu1351Val missense NM_001407862.1:c.3854A>T NP_001394791.1:p.Glu1285Val missense NM_001407863.1:c.3932A>T NP_001394792.1:p.Glu1311Val missense NM_001407874.1:c.3851A>T NP_001394803.1:p.Glu1284Val missense NM_001407875.1:c.3851A>T NP_001394804.1:p.Glu1284Val missense NM_001407879.1:c.3845A>T NP_001394808.1:p.Glu1282Val missense NM_001407881.1:c.3845A>T NP_001394810.1:p.Glu1282Val missense NM_001407882.1:c.3845A>T NP_001394811.1:p.Glu1282Val missense NM_001407884.1:c.3845A>T NP_001394813.1:p.Glu1282Val missense NM_001407885.1:c.3845A>T NP_001394814.1:p.Glu1282Val missense NM_001407886.1:c.3845A>T NP_001394815.1:p.Glu1282Val missense NM_001407887.1:c.3845A>T NP_001394816.1:p.Glu1282Val missense NM_001407889.1:c.3845A>T NP_001394818.1:p.Glu1282Val missense NM_001407894.1:c.3842A>T NP_001394823.1:p.Glu1281Val missense NM_001407895.1:c.3842A>T NP_001394824.1:p.Glu1281Val missense NM_001407896.1:c.3842A>T NP_001394825.1:p.Glu1281Val missense NM_001407897.1:c.3842A>T NP_001394826.1:p.Glu1281Val missense NM_001407898.1:c.3842A>T NP_001394827.1:p.Glu1281Val missense NM_001407899.1:c.3842A>T NP_001394828.1:p.Glu1281Val missense NM_001407900.1:c.3845A>T NP_001394829.1:p.Glu1282Val missense NM_001407902.1:c.3845A>T NP_001394831.1:p.Glu1282Val missense NM_001407904.1:c.3845A>T NP_001394833.1:p.Glu1282Val missense NM_001407906.1:c.3845A>T NP_001394835.1:p.Glu1282Val missense NM_001407907.1:c.3845A>T NP_001394836.1:p.Glu1282Val missense NM_001407908.1:c.3845A>T NP_001394837.1:p.Glu1282Val missense NM_001407909.1:c.3845A>T NP_001394838.1:p.Glu1282Val missense NM_001407910.1:c.3845A>T NP_001394839.1:p.Glu1282Val missense NM_001407915.1:c.3842A>T NP_001394844.1:p.Glu1281Val missense NM_001407916.1:c.3842A>T NP_001394845.1:p.Glu1281Val missense NM_001407917.1:c.3842A>T NP_001394846.1:p.Glu1281Val missense NM_001407918.1:c.3842A>T NP_001394847.1:p.Glu1281Val missense NM_001407919.1:c.3932A>T NP_001394848.1:p.Glu1311Val missense NM_001407920.1:c.3791A>T NP_001394849.1:p.Glu1264Val missense NM_001407921.1:c.3791A>T NP_001394850.1:p.Glu1264Val missense NM_001407922.1:c.3791A>T NP_001394851.1:p.Glu1264Val missense NM_001407923.1:c.3791A>T NP_001394852.1:p.Glu1264Val missense NM_001407924.1:c.3791A>T NP_001394853.1:p.Glu1264Val missense NM_001407925.1:c.3791A>T NP_001394854.1:p.Glu1264Val missense NM_001407926.1:c.3791A>T NP_001394855.1:p.Glu1264Val missense NM_001407927.1:c.3791A>T NP_001394856.1:p.Glu1264Val missense NM_001407928.1:c.3791A>T NP_001394857.1:p.Glu1264Val missense NM_001407929.1:c.3791A>T NP_001394858.1:p.Glu1264Val missense NM_001407930.1:c.3788A>T NP_001394859.1:p.Glu1263Val missense NM_001407931.1:c.3788A>T NP_001394860.1:p.Glu1263Val missense NM_001407932.1:c.3788A>T NP_001394861.1:p.Glu1263Val missense NM_001407933.1:c.3791A>T NP_001394862.1:p.Glu1264Val missense NM_001407934.1:c.3788A>T NP_001394863.1:p.Glu1263Val missense NM_001407935.1:c.3791A>T NP_001394864.1:p.Glu1264Val missense NM_001407936.1:c.3788A>T NP_001394865.1:p.Glu1263Val missense NM_001407937.1:c.3932A>T NP_001394866.1:p.Glu1311Val missense NM_001407938.1:c.3932A>T NP_001394867.1:p.Glu1311Val missense NM_001407939.1:c.3932A>T NP_001394868.1:p.Glu1311Val missense NM_001407940.1:c.3929A>T NP_001394869.1:p.Glu1310Val missense NM_001407941.1:c.3929A>T NP_001394870.1:p.Glu1310Val missense NM_001407942.1:c.3914A>T NP_001394871.1:p.Glu1305Val missense NM_001407943.1:c.3911A>T NP_001394872.1:p.Glu1304Val missense NM_001407944.1:c.3914A>T NP_001394873.1:p.Glu1305Val missense NM_001407945.1:c.3914A>T NP_001394874.1:p.Glu1305Val missense NM_001407946.1:c.3722A>T NP_001394875.1:p.Glu1241Val missense NM_001407947.1:c.3722A>T NP_001394876.1:p.Glu1241Val missense NM_001407948.1:c.3722A>T NP_001394877.1:p.Glu1241Val missense NM_001407949.1:c.3722A>T NP_001394878.1:p.Glu1241Val missense NM_001407950.1:c.3722A>T NP_001394879.1:p.Glu1241Val missense NM_001407951.1:c.3722A>T NP_001394880.1:p.Glu1241Val missense NM_001407952.1:c.3722A>T NP_001394881.1:p.Glu1241Val missense NM_001407953.1:c.3722A>T NP_001394882.1:p.Glu1241Val missense NM_001407954.1:c.3719A>T NP_001394883.1:p.Glu1240Val missense NM_001407955.1:c.3719A>T NP_001394884.1:p.Glu1240Val missense NM_001407956.1:c.3719A>T NP_001394885.1:p.Glu1240Val missense NM_001407957.1:c.3722A>T NP_001394886.1:p.Glu1241Val missense NM_001407958.1:c.3719A>T NP_001394887.1:p.Glu1240Val missense NM_001407959.1:c.3674A>T NP_001394888.1:p.Glu1225Val missense NM_001407960.1:c.3674A>T NP_001394889.1:p.Glu1225Val missense NM_001407962.1:c.3671A>T NP_001394891.1:p.Glu1224Val missense NM_001407963.1:c.3674A>T NP_001394892.1:p.Glu1225Val missense NM_001407964.1:c.3911A>T NP_001394893.1:p.Glu1304Val missense NM_001407965.1:c.3551A>T NP_001394894.1:p.Glu1184Val missense NM_001407966.1:c.3167A>T NP_001394895.1:p.Glu1056Val missense NM_001407967.1:c.3167A>T NP_001394896.1:p.Glu1056Val missense NM_001407968.1:c.1451A>T NP_001394897.1:p.Glu484Val missense NM_001407969.1:c.1451A>T NP_001394898.1:p.Glu484Val missense NM_001407970.1:c.788-444A>T intron variant NM_001407971.1:c.788-444A>T intron variant NM_001407972.1:c.785-444A>T intron variant NM_001407973.1:c.788-444A>T intron variant NM_001407974.1:c.788-444A>T intron variant NM_001407975.1:c.788-444A>T intron variant NM_001407976.1:c.788-444A>T intron variant NM_001407977.1:c.788-444A>T intron variant NM_001407978.1:c.788-444A>T intron variant NM_001407979.1:c.788-444A>T intron variant NM_001407980.1:c.788-444A>T intron variant NM_001407981.1:c.788-444A>T intron variant NM_001407982.1:c.788-444A>T intron variant NM_001407983.1:c.788-444A>T intron variant NM_001407984.1:c.785-444A>T intron variant NM_001407985.1:c.785-444A>T intron variant NM_001407986.1:c.785-444A>T intron variant NM_001407990.1:c.788-444A>T intron variant NM_001407991.1:c.785-444A>T intron variant NM_001407992.1:c.785-444A>T intron variant NM_001407993.1:c.788-444A>T intron variant NM_001408392.1:c.785-444A>T intron variant NM_001408396.1:c.785-444A>T intron variant NM_001408397.1:c.785-444A>T intron variant NM_001408398.1:c.785-444A>T intron variant NM_001408399.1:c.785-444A>T intron variant NM_001408400.1:c.785-444A>T intron variant NM_001408401.1:c.785-444A>T intron variant NM_001408402.1:c.785-444A>T intron variant NM_001408403.1:c.788-444A>T intron variant NM_001408404.1:c.788-444A>T intron variant NM_001408406.1:c.791-453A>T intron variant NM_001408407.1:c.785-444A>T intron variant NM_001408408.1:c.779-444A>T intron variant NM_001408409.1:c.710-444A>T intron variant NM_001408410.1:c.647-444A>T intron variant NM_001408411.1:c.710-444A>T intron variant NM_001408412.1:c.710-444A>T intron variant NM_001408413.1:c.707-444A>T intron variant NM_001408414.1:c.710-444A>T intron variant NM_001408415.1:c.710-444A>T intron variant NM_001408416.1:c.707-444A>T intron variant NM_001408418.1:c.671-444A>T intron variant NM_001408419.1:c.671-444A>T intron variant NM_001408420.1:c.671-444A>T intron variant NM_001408421.1:c.668-444A>T intron variant NM_001408422.1:c.671-444A>T intron variant NM_001408423.1:c.671-444A>T intron variant NM_001408424.1:c.668-444A>T intron variant NM_001408425.1:c.665-444A>T intron variant NM_001408426.1:c.665-444A>T intron variant NM_001408427.1:c.665-444A>T intron variant NM_001408428.1:c.665-444A>T intron variant NM_001408429.1:c.665-444A>T intron variant NM_001408430.1:c.665-444A>T intron variant NM_001408431.1:c.668-444A>T intron variant NM_001408432.1:c.662-444A>T intron variant NM_001408433.1:c.662-444A>T intron variant NM_001408434.1:c.662-444A>T intron variant NM_001408435.1:c.662-444A>T intron variant NM_001408436.1:c.665-444A>T intron variant NM_001408437.1:c.665-444A>T intron variant NM_001408438.1:c.665-444A>T intron variant NM_001408439.1:c.665-444A>T intron variant NM_001408440.1:c.665-444A>T intron variant NM_001408441.1:c.665-444A>T intron variant NM_001408442.1:c.665-444A>T intron variant NM_001408443.1:c.665-444A>T intron variant NM_001408444.1:c.665-444A>T intron variant NM_001408445.1:c.662-444A>T intron variant NM_001408446.1:c.662-444A>T intron variant NM_001408447.1:c.662-444A>T intron variant NM_001408448.1:c.662-444A>T intron variant NM_001408450.1:c.662-444A>T intron variant NM_001408451.1:c.653-444A>T intron variant NM_001408452.1:c.647-444A>T intron variant NM_001408453.1:c.647-444A>T intron variant NM_001408454.1:c.647-444A>T intron variant NM_001408455.1:c.647-444A>T intron variant NM_001408456.1:c.647-444A>T intron variant NM_001408457.1:c.647-444A>T intron variant NM_001408458.1:c.647-444A>T intron variant NM_001408459.1:c.647-444A>T intron variant NM_001408460.1:c.647-444A>T intron variant NM_001408461.1:c.647-444A>T intron variant NM_001408462.1:c.644-444A>T intron variant NM_001408463.1:c.644-444A>T intron variant NM_001408464.1:c.644-444A>T intron variant NM_001408465.1:c.644-444A>T intron variant NM_001408466.1:c.647-444A>T intron variant NM_001408467.1:c.647-444A>T intron variant NM_001408468.1:c.644-444A>T intron variant NM_001408469.1:c.647-444A>T intron variant NM_001408470.1:c.644-444A>T intron variant NM_001408472.1:c.788-444A>T intron variant NM_001408473.1:c.785-444A>T intron variant NM_001408474.1:c.587-444A>T intron variant NM_001408475.1:c.584-444A>T intron variant NM_001408476.1:c.587-444A>T intron variant NM_001408478.1:c.578-444A>T intron variant NM_001408479.1:c.578-444A>T intron variant NM_001408480.1:c.578-444A>T intron variant NM_001408481.1:c.578-444A>T intron variant NM_001408482.1:c.578-444A>T intron variant NM_001408483.1:c.578-444A>T intron variant NM_001408484.1:c.578-444A>T intron variant NM_001408485.1:c.578-444A>T intron variant NM_001408489.1:c.578-444A>T intron variant NM_001408490.1:c.575-444A>T intron variant NM_001408491.1:c.575-444A>T intron variant NM_001408492.1:c.578-444A>T intron variant NM_001408493.1:c.575-444A>T intron variant NM_001408494.1:c.548-444A>T intron variant NM_001408495.1:c.545-444A>T intron variant NM_001408496.1:c.524-444A>T intron variant NM_001408497.1:c.524-444A>T intron variant NM_001408498.1:c.524-444A>T intron variant NM_001408499.1:c.524-444A>T intron variant NM_001408500.1:c.524-444A>T intron variant NM_001408501.1:c.524-444A>T intron variant NM_001408502.1:c.455-444A>T intron variant NM_001408503.1:c.521-444A>T intron variant NM_001408504.1:c.521-444A>T intron variant NM_001408505.1:c.521-444A>T intron variant NM_001408506.1:c.461-444A>T intron variant NM_001408507.1:c.461-444A>T intron variant NM_001408508.1:c.452-444A>T intron variant NM_001408509.1:c.452-444A>T intron variant NM_001408510.1:c.407-444A>T intron variant NM_001408511.1:c.404-444A>T intron variant NM_001408512.1:c.284-444A>T intron variant NM_001408513.1:c.578-444A>T intron variant NM_001408514.1:c.578-444A>T intron variant NM_007297.4:c.3914A>T NP_009228.2:p.Glu1305Val missense NM_007298.4:c.788-444A>T intron variant NM_007299.4:c.788-444A>T intron variant NM_007300.4:c.4055A>T NP_009231.2:p.Glu1352Val missense NR_027676.1:n.4191A>T NC_000017.11:g.43091476T>A NC_000017.10:g.41243493T>A NG_005905.2:g.126508A>T NG_087068.1:g.458T>A LRG_292:g.126508A>T LRG_292t1:c.4055A>T LRG_292p1:p.Glu1352Val - Protein change
- E1352V, E1305V, E1284V, E1326V, E1184V, E1240V, E1241V, E1281V, E1304V, E1311V, E1224V, E1225V, E1263V, E1282V, E1285V, E1349V, E1056V, E1264V, E1310V, E1325V, E1351V, E484V
- Other names
- -
- Canonical SPDI
- NC_000017.11:43091475:T:A
-
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 |
13044 | 14850 | |
| LOC126862571 | - | - | - | GRCh38 | - | 1651 |
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 (2) |
criteria provided, multiple submitters, no conflicts
|
May 1, 2019 | RCV000235734.24 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Dec 6, 2023 | RCV000637763.10 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Feb 19, 2024 | RCV003157493.5 | |
| Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Mar 8, 2024 | RCV003998925.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 17, 2024 | RCV003987475.1 |
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
(Feb 03, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000293903.9
First in ClinVar: Jul 25, 2016 Last updated: Jul 25, 2016 |
Comment:
This variant is denoted BRCA1 c.4055A>T at the cDNA level, p.Glu1352Val (E1352V) at the protein level, and results in the change of a Glutamic Acid … (more)
This variant is denoted BRCA1 c.4055A>T at the cDNA level, p.Glu1352Val (E1352V) at the protein level, and results in the change of a Glutamic Acid to a Valine (GAA>GTA). Using alternate nomenclature, this variant would be defined as BRCA1 4174A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu1352Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1352Val occurs at a position that is not conserved and is located in the SCD domain as well as a region known to interact with multiple proteins (Narod 2004, Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Glu1352Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
|
|
|
Uncertain significance
(Dec 06, 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: SCV000759240.8
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1352 of the BRCA1 protein … (more)
This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1352 of the BRCA1 protein (p.Glu1352Val). 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: 246375). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. 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
(Jan 17, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004803503.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
|
|
|
Likely Benign
(Mar 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004822660.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 1
|
|
|
Uncertain significance
(Feb 19, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV005025892.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.E1352V variant (also known as c.4055A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide … (more)
The p.E1352V variant (also known as c.4055A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 4055. The glutamic acid at codon 1352 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Mar 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005058233.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
|
Uncertain significance
(May 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001151327.27
First in ClinVar: Feb 03, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 2
|
|
|
Likely benign
(Mar 23, 2023)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV003851481.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023
Comment:
BRCA1 coldspot (exon 11 using historical exon numbering). Reclassification based on statistical prior probability
|
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
|
Comment:
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1352 of the BRCA1 protein (p.Glu1352Val). 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: 246375). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. 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.E1352V variant (also known as c.4055A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 4055. The glutamic acid at codon 1352 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
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 variant is denoted BRCA1 c.4055A>T at the cDNA level, p.Glu1352Val (E1352V) at the protein level, and results in the change of a Glutamic Acid to a Valine (GAA>GTA). Using alternate nomenclature, this variant would be defined as BRCA1 4174A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu1352Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Valine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1352Val occurs at a position that is not conserved and is located in the SCD domain as well as a region known to interact with multiple proteins (Narod 2004, Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Glu1352Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Comment:
This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1352 of the BRCA1 protein (p.Glu1352Val). 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: 246375). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function with a negative predictive value of 95%. 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.E1352V variant (also known as c.4055A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 4055. The glutamic acid at codon 1352 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots". | Dines JN | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 31911673 |
Text-mined citations for rs879254228 ...
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Record last updated Oct 20, 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.