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. 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. ClinVar contains an entry for this variant (Variation ID: 240769). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 367 of the BRCA1 protein (p.Thr367Ala).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.1099A>G (p.Thr367Ala)
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.
(7)
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.
Conflicting classifications of pathogenicity
Uncertain significance(5); Likely benign(2)
Uncertain significance(5); Likely benign(2)
7
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.1099A>G (p.Thr367Ala)
Variation ID: 240769 Accession: VCV000240769.24
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43094432 (GRCh38) [ NCBI UCSC ] 17: 41246449 (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 Dec 6, 2016 Oct 20, 2024 Jul 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.1099A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Thr367Ala missense NM_001407571.1:c.886A>G NP_001394500.1:p.Thr296Ala missense NM_001407581.1:c.1099A>G NP_001394510.1:p.Thr367Ala missense NM_001407582.1:c.1099A>G NP_001394511.1:p.Thr367Ala missense NM_001407583.1:c.1099A>G NP_001394512.1:p.Thr367Ala missense NM_001407585.1:c.1099A>G NP_001394514.1:p.Thr367Ala missense NM_001407587.1:c.1096A>G NP_001394516.1:p.Thr366Ala missense NM_001407590.1:c.1096A>G NP_001394519.1:p.Thr366Ala missense NM_001407591.1:c.1096A>G NP_001394520.1:p.Thr366Ala missense NM_001407593.1:c.1099A>G NP_001394522.1:p.Thr367Ala missense NM_001407594.1:c.1099A>G NP_001394523.1:p.Thr367Ala missense NM_001407596.1:c.1099A>G NP_001394525.1:p.Thr367Ala missense NM_001407597.1:c.1099A>G NP_001394526.1:p.Thr367Ala missense NM_001407598.1:c.1099A>G NP_001394527.1:p.Thr367Ala missense NM_001407602.1:c.1099A>G NP_001394531.1:p.Thr367Ala missense NM_001407603.1:c.1099A>G NP_001394532.1:p.Thr367Ala missense NM_001407605.1:c.1099A>G NP_001394534.1:p.Thr367Ala missense NM_001407610.1:c.1096A>G NP_001394539.1:p.Thr366Ala missense NM_001407611.1:c.1096A>G NP_001394540.1:p.Thr366Ala missense NM_001407612.1:c.1096A>G NP_001394541.1:p.Thr366Ala missense NM_001407613.1:c.1096A>G NP_001394542.1:p.Thr366Ala missense NM_001407614.1:c.1096A>G NP_001394543.1:p.Thr366Ala missense NM_001407615.1:c.1096A>G NP_001394544.1:p.Thr366Ala missense NM_001407616.1:c.1099A>G NP_001394545.1:p.Thr367Ala missense NM_001407617.1:c.1099A>G NP_001394546.1:p.Thr367Ala missense NM_001407618.1:c.1099A>G NP_001394547.1:p.Thr367Ala missense NM_001407619.1:c.1099A>G NP_001394548.1:p.Thr367Ala missense NM_001407620.1:c.1099A>G NP_001394549.1:p.Thr367Ala missense NM_001407621.1:c.1099A>G NP_001394550.1:p.Thr367Ala missense NM_001407622.1:c.1099A>G NP_001394551.1:p.Thr367Ala missense NM_001407623.1:c.1099A>G NP_001394552.1:p.Thr367Ala missense NM_001407624.1:c.1099A>G NP_001394553.1:p.Thr367Ala missense NM_001407625.1:c.1099A>G NP_001394554.1:p.Thr367Ala missense NM_001407626.1:c.1099A>G NP_001394555.1:p.Thr367Ala missense NM_001407627.1:c.1096A>G NP_001394556.1:p.Thr366Ala missense NM_001407628.1:c.1096A>G NP_001394557.1:p.Thr366Ala missense NM_001407629.1:c.1096A>G NP_001394558.1:p.Thr366Ala missense NM_001407630.1:c.1096A>G NP_001394559.1:p.Thr366Ala missense NM_001407631.1:c.1096A>G NP_001394560.1:p.Thr366Ala missense NM_001407632.1:c.1096A>G NP_001394561.1:p.Thr366Ala missense NM_001407633.1:c.1096A>G NP_001394562.1:p.Thr366Ala missense NM_001407634.1:c.1096A>G NP_001394563.1:p.Thr366Ala missense NM_001407635.1:c.1096A>G NP_001394564.1:p.Thr366Ala missense NM_001407636.1:c.1096A>G NP_001394565.1:p.Thr366Ala missense NM_001407637.1:c.1096A>G NP_001394566.1:p.Thr366Ala missense NM_001407638.1:c.1096A>G NP_001394567.1:p.Thr366Ala missense NM_001407639.1:c.1099A>G NP_001394568.1:p.Thr367Ala missense NM_001407640.1:c.1099A>G NP_001394569.1:p.Thr367Ala missense NM_001407641.1:c.1099A>G NP_001394570.1:p.Thr367Ala missense NM_001407642.1:c.1099A>G NP_001394571.1:p.Thr367Ala missense NM_001407644.1:c.1096A>G NP_001394573.1:p.Thr366Ala missense NM_001407645.1:c.1096A>G NP_001394574.1:p.Thr366Ala missense NM_001407646.1:c.1090A>G NP_001394575.1:p.Thr364Ala missense NM_001407647.1:c.1090A>G NP_001394576.1:p.Thr364Ala missense NM_001407648.1:c.976A>G NP_001394577.1:p.Thr326Ala missense NM_001407649.1:c.973A>G NP_001394578.1:p.Thr325Ala missense NM_001407652.1:c.1099A>G NP_001394581.1:p.Thr367Ala missense NM_001407653.1:c.1021A>G NP_001394582.1:p.Thr341Ala missense NM_001407654.1:c.1021A>G NP_001394583.1:p.Thr341Ala missense NM_001407655.1:c.1021A>G NP_001394584.1:p.Thr341Ala missense NM_001407656.1:c.1021A>G NP_001394585.1:p.Thr341Ala missense NM_001407657.1:c.1021A>G NP_001394586.1:p.Thr341Ala missense NM_001407658.1:c.1021A>G NP_001394587.1:p.Thr341Ala missense NM_001407659.1:c.1018A>G NP_001394588.1:p.Thr340Ala missense NM_001407660.1:c.1018A>G NP_001394589.1:p.Thr340Ala missense NM_001407661.1:c.1018A>G NP_001394590.1:p.Thr340Ala missense NM_001407662.1:c.1018A>G NP_001394591.1:p.Thr340Ala missense NM_001407663.1:c.1021A>G NP_001394592.1:p.Thr341Ala missense NM_001407664.1:c.976A>G NP_001394593.1:p.Thr326Ala missense NM_001407665.1:c.976A>G NP_001394594.1:p.Thr326Ala missense NM_001407666.1:c.976A>G NP_001394595.1:p.Thr326Ala missense NM_001407667.1:c.976A>G NP_001394596.1:p.Thr326Ala missense NM_001407668.1:c.976A>G NP_001394597.1:p.Thr326Ala missense NM_001407669.1:c.976A>G NP_001394598.1:p.Thr326Ala missense NM_001407670.1:c.973A>G NP_001394599.1:p.Thr325Ala missense NM_001407671.1:c.973A>G NP_001394600.1:p.Thr325Ala missense NM_001407672.1:c.973A>G NP_001394601.1:p.Thr325Ala missense NM_001407673.1:c.973A>G NP_001394602.1:p.Thr325Ala missense NM_001407674.1:c.976A>G NP_001394603.1:p.Thr326Ala missense NM_001407675.1:c.976A>G NP_001394604.1:p.Thr326Ala missense NM_001407676.1:c.976A>G NP_001394605.1:p.Thr326Ala missense NM_001407677.1:c.976A>G NP_001394606.1:p.Thr326Ala missense NM_001407678.1:c.976A>G NP_001394607.1:p.Thr326Ala missense NM_001407679.1:c.976A>G NP_001394608.1:p.Thr326Ala missense NM_001407680.1:c.976A>G NP_001394609.1:p.Thr326Ala missense NM_001407681.1:c.976A>G NP_001394610.1:p.Thr326Ala missense NM_001407682.1:c.976A>G NP_001394611.1:p.Thr326Ala missense NM_001407683.1:c.976A>G NP_001394612.1:p.Thr326Ala missense NM_001407684.1:c.1099A>G NP_001394613.1:p.Thr367Ala missense NM_001407685.1:c.973A>G NP_001394614.1:p.Thr325Ala missense NM_001407686.1:c.973A>G NP_001394615.1:p.Thr325Ala missense NM_001407687.1:c.973A>G NP_001394616.1:p.Thr325Ala missense NM_001407688.1:c.973A>G NP_001394617.1:p.Thr325Ala missense NM_001407689.1:c.973A>G NP_001394618.1:p.Thr325Ala missense NM_001407690.1:c.973A>G NP_001394619.1:p.Thr325Ala missense NM_001407691.1:c.973A>G NP_001394620.1:p.Thr325Ala missense NM_001407692.1:c.958A>G NP_001394621.1:p.Thr320Ala missense NM_001407694.1:c.958A>G NP_001394623.1:p.Thr320Ala missense NM_001407695.1:c.958A>G NP_001394624.1:p.Thr320Ala missense NM_001407696.1:c.958A>G NP_001394625.1:p.Thr320Ala missense NM_001407697.1:c.958A>G NP_001394626.1:p.Thr320Ala missense NM_001407698.1:c.958A>G NP_001394627.1:p.Thr320Ala missense NM_001407724.1:c.958A>G NP_001394653.1:p.Thr320Ala missense NM_001407725.1:c.958A>G NP_001394654.1:p.Thr320Ala missense NM_001407726.1:c.958A>G NP_001394655.1:p.Thr320Ala missense NM_001407727.1:c.958A>G NP_001394656.1:p.Thr320Ala missense NM_001407728.1:c.958A>G NP_001394657.1:p.Thr320Ala missense NM_001407729.1:c.958A>G NP_001394658.1:p.Thr320Ala missense NM_001407730.1:c.958A>G NP_001394659.1:p.Thr320Ala missense NM_001407731.1:c.958A>G NP_001394660.1:p.Thr320Ala missense NM_001407732.1:c.958A>G NP_001394661.1:p.Thr320Ala missense NM_001407733.1:c.958A>G NP_001394662.1:p.Thr320Ala missense NM_001407734.1:c.958A>G NP_001394663.1:p.Thr320Ala missense NM_001407735.1:c.958A>G NP_001394664.1:p.Thr320Ala missense NM_001407736.1:c.958A>G NP_001394665.1:p.Thr320Ala missense NM_001407737.1:c.958A>G NP_001394666.1:p.Thr320Ala missense NM_001407738.1:c.958A>G NP_001394667.1:p.Thr320Ala missense NM_001407739.1:c.958A>G NP_001394668.1:p.Thr320Ala missense NM_001407740.1:c.955A>G NP_001394669.1:p.Thr319Ala missense NM_001407741.1:c.955A>G NP_001394670.1:p.Thr319Ala missense NM_001407742.1:c.955A>G NP_001394671.1:p.Thr319Ala missense NM_001407743.1:c.955A>G NP_001394672.1:p.Thr319Ala missense NM_001407744.1:c.955A>G NP_001394673.1:p.Thr319Ala missense NM_001407745.1:c.955A>G NP_001394674.1:p.Thr319Ala missense NM_001407746.1:c.955A>G NP_001394675.1:p.Thr319Ala missense NM_001407747.1:c.955A>G NP_001394676.1:p.Thr319Ala missense NM_001407748.1:c.955A>G NP_001394677.1:p.Thr319Ala missense NM_001407749.1:c.955A>G NP_001394678.1:p.Thr319Ala missense NM_001407750.1:c.958A>G NP_001394679.1:p.Thr320Ala missense NM_001407751.1:c.958A>G NP_001394680.1:p.Thr320Ala missense NM_001407752.1:c.958A>G NP_001394681.1:p.Thr320Ala missense NM_001407838.1:c.955A>G NP_001394767.1:p.Thr319Ala missense NM_001407839.1:c.955A>G NP_001394768.1:p.Thr319Ala missense NM_001407841.1:c.955A>G NP_001394770.1:p.Thr319Ala missense NM_001407842.1:c.955A>G NP_001394771.1:p.Thr319Ala missense NM_001407843.1:c.955A>G NP_001394772.1:p.Thr319Ala missense NM_001407844.1:c.955A>G NP_001394773.1:p.Thr319Ala missense NM_001407845.1:c.955A>G NP_001394774.1:p.Thr319Ala missense NM_001407846.1:c.955A>G NP_001394775.1:p.Thr319Ala missense NM_001407847.1:c.955A>G NP_001394776.1:p.Thr319Ala missense NM_001407848.1:c.955A>G NP_001394777.1:p.Thr319Ala missense NM_001407849.1:c.955A>G NP_001394778.1:p.Thr319Ala missense NM_001407850.1:c.958A>G NP_001394779.1:p.Thr320Ala missense NM_001407851.1:c.958A>G NP_001394780.1:p.Thr320Ala missense NM_001407852.1:c.958A>G NP_001394781.1:p.Thr320Ala missense NM_001407853.1:c.886A>G NP_001394782.1:p.Thr296Ala missense NM_001407854.1:c.1099A>G NP_001394783.1:p.Thr367Ala missense NM_001407858.1:c.1099A>G NP_001394787.1:p.Thr367Ala missense NM_001407859.1:c.1099A>G NP_001394788.1:p.Thr367Ala missense NM_001407860.1:c.1096A>G NP_001394789.1:p.Thr366Ala missense NM_001407861.1:c.1096A>G NP_001394790.1:p.Thr366Ala missense NM_001407862.1:c.898A>G NP_001394791.1:p.Thr300Ala missense NM_001407863.1:c.976A>G NP_001394792.1:p.Thr326Ala missense NM_001407874.1:c.895A>G NP_001394803.1:p.Thr299Ala missense NM_001407875.1:c.895A>G NP_001394804.1:p.Thr299Ala missense NM_001407879.1:c.889A>G NP_001394808.1:p.Thr297Ala missense NM_001407881.1:c.889A>G NP_001394810.1:p.Thr297Ala missense NM_001407882.1:c.889A>G NP_001394811.1:p.Thr297Ala missense NM_001407884.1:c.889A>G NP_001394813.1:p.Thr297Ala missense NM_001407885.1:c.889A>G NP_001394814.1:p.Thr297Ala missense NM_001407886.1:c.889A>G NP_001394815.1:p.Thr297Ala missense NM_001407887.1:c.889A>G NP_001394816.1:p.Thr297Ala missense NM_001407889.1:c.889A>G NP_001394818.1:p.Thr297Ala missense NM_001407894.1:c.886A>G NP_001394823.1:p.Thr296Ala missense NM_001407895.1:c.886A>G NP_001394824.1:p.Thr296Ala missense NM_001407896.1:c.886A>G NP_001394825.1:p.Thr296Ala missense NM_001407897.1:c.886A>G NP_001394826.1:p.Thr296Ala missense NM_001407898.1:c.886A>G NP_001394827.1:p.Thr296Ala missense NM_001407899.1:c.886A>G NP_001394828.1:p.Thr296Ala missense NM_001407900.1:c.889A>G NP_001394829.1:p.Thr297Ala missense NM_001407902.1:c.889A>G NP_001394831.1:p.Thr297Ala missense NM_001407904.1:c.889A>G NP_001394833.1:p.Thr297Ala missense NM_001407906.1:c.889A>G NP_001394835.1:p.Thr297Ala missense NM_001407907.1:c.889A>G NP_001394836.1:p.Thr297Ala missense NM_001407908.1:c.889A>G NP_001394837.1:p.Thr297Ala missense NM_001407909.1:c.889A>G NP_001394838.1:p.Thr297Ala missense NM_001407910.1:c.889A>G NP_001394839.1:p.Thr297Ala missense NM_001407915.1:c.886A>G NP_001394844.1:p.Thr296Ala missense NM_001407916.1:c.886A>G NP_001394845.1:p.Thr296Ala missense NM_001407917.1:c.886A>G NP_001394846.1:p.Thr296Ala missense NM_001407918.1:c.886A>G NP_001394847.1:p.Thr296Ala missense NM_001407919.1:c.976A>G NP_001394848.1:p.Thr326Ala missense NM_001407920.1:c.835A>G NP_001394849.1:p.Thr279Ala missense NM_001407921.1:c.835A>G NP_001394850.1:p.Thr279Ala missense NM_001407922.1:c.835A>G NP_001394851.1:p.Thr279Ala missense NM_001407923.1:c.835A>G NP_001394852.1:p.Thr279Ala missense NM_001407924.1:c.835A>G NP_001394853.1:p.Thr279Ala missense NM_001407925.1:c.835A>G NP_001394854.1:p.Thr279Ala missense NM_001407926.1:c.835A>G NP_001394855.1:p.Thr279Ala missense NM_001407927.1:c.835A>G NP_001394856.1:p.Thr279Ala missense NM_001407928.1:c.835A>G NP_001394857.1:p.Thr279Ala missense NM_001407929.1:c.835A>G NP_001394858.1:p.Thr279Ala missense NM_001407930.1:c.832A>G NP_001394859.1:p.Thr278Ala missense NM_001407931.1:c.832A>G NP_001394860.1:p.Thr278Ala missense NM_001407932.1:c.832A>G NP_001394861.1:p.Thr278Ala missense NM_001407933.1:c.835A>G NP_001394862.1:p.Thr279Ala missense NM_001407934.1:c.832A>G NP_001394863.1:p.Thr278Ala missense NM_001407935.1:c.835A>G NP_001394864.1:p.Thr279Ala missense NM_001407936.1:c.832A>G NP_001394865.1:p.Thr278Ala missense NM_001407937.1:c.976A>G NP_001394866.1:p.Thr326Ala missense NM_001407938.1:c.976A>G NP_001394867.1:p.Thr326Ala missense NM_001407939.1:c.976A>G NP_001394868.1:p.Thr326Ala missense NM_001407940.1:c.973A>G NP_001394869.1:p.Thr325Ala missense NM_001407941.1:c.973A>G NP_001394870.1:p.Thr325Ala missense NM_001407942.1:c.958A>G NP_001394871.1:p.Thr320Ala missense NM_001407943.1:c.955A>G NP_001394872.1:p.Thr319Ala missense NM_001407944.1:c.958A>G NP_001394873.1:p.Thr320Ala missense NM_001407945.1:c.958A>G NP_001394874.1:p.Thr320Ala missense NM_001407946.1:c.766A>G NP_001394875.1:p.Thr256Ala missense NM_001407947.1:c.766A>G NP_001394876.1:p.Thr256Ala missense NM_001407948.1:c.766A>G NP_001394877.1:p.Thr256Ala missense NM_001407949.1:c.766A>G NP_001394878.1:p.Thr256Ala missense NM_001407950.1:c.766A>G NP_001394879.1:p.Thr256Ala missense NM_001407951.1:c.766A>G NP_001394880.1:p.Thr256Ala missense NM_001407952.1:c.766A>G NP_001394881.1:p.Thr256Ala missense NM_001407953.1:c.766A>G NP_001394882.1:p.Thr256Ala missense NM_001407954.1:c.763A>G NP_001394883.1:p.Thr255Ala missense NM_001407955.1:c.763A>G NP_001394884.1:p.Thr255Ala missense NM_001407956.1:c.763A>G NP_001394885.1:p.Thr255Ala missense NM_001407957.1:c.766A>G NP_001394886.1:p.Thr256Ala missense NM_001407958.1:c.763A>G NP_001394887.1:p.Thr255Ala missense NM_001407959.1:c.718A>G NP_001394888.1:p.Thr240Ala missense NM_001407960.1:c.718A>G NP_001394889.1:p.Thr240Ala missense NM_001407962.1:c.715A>G NP_001394891.1:p.Thr239Ala missense NM_001407963.1:c.718A>G NP_001394892.1:p.Thr240Ala missense NM_001407964.1:c.955A>G NP_001394893.1:p.Thr319Ala missense NM_001407965.1:c.595A>G NP_001394894.1:p.Thr199Ala missense NM_001407966.1:c.211A>G NP_001394895.1:p.Thr71Ala missense NM_001407967.1:c.211A>G NP_001394896.1:p.Thr71Ala missense NM_001407968.1:c.787+312A>G intron variant NM_001407969.1:c.787+312A>G intron variant NM_001407970.1:c.787+312A>G intron variant NM_001407971.1:c.787+312A>G intron variant NM_001407972.1:c.784+312A>G intron variant NM_001407973.1:c.787+312A>G intron variant NM_001407974.1:c.787+312A>G intron variant NM_001407975.1:c.787+312A>G intron variant NM_001407976.1:c.787+312A>G intron variant NM_001407977.1:c.787+312A>G intron variant NM_001407978.1:c.787+312A>G intron variant NM_001407979.1:c.787+312A>G intron variant NM_001407980.1:c.787+312A>G intron variant NM_001407981.1:c.787+312A>G intron variant NM_001407982.1:c.787+312A>G intron variant NM_001407983.1:c.787+312A>G intron variant NM_001407984.1:c.784+312A>G intron variant NM_001407985.1:c.784+312A>G intron variant NM_001407986.1:c.784+312A>G intron variant NM_001407990.1:c.787+312A>G intron variant NM_001407991.1:c.784+312A>G intron variant NM_001407992.1:c.784+312A>G intron variant NM_001407993.1:c.787+312A>G intron variant NM_001408392.1:c.784+312A>G intron variant NM_001408396.1:c.784+312A>G intron variant NM_001408397.1:c.784+312A>G intron variant NM_001408398.1:c.784+312A>G intron variant NM_001408399.1:c.784+312A>G intron variant NM_001408400.1:c.784+312A>G intron variant NM_001408401.1:c.784+312A>G intron variant NM_001408402.1:c.784+312A>G intron variant NM_001408403.1:c.787+312A>G intron variant NM_001408404.1:c.787+312A>G intron variant NM_001408406.1:c.790+309A>G intron variant NM_001408407.1:c.784+312A>G intron variant NM_001408408.1:c.778+312A>G intron variant NM_001408409.1:c.709+312A>G intron variant NM_001408410.1:c.646+312A>G intron variant NM_001408411.1:c.709+312A>G intron variant NM_001408412.1:c.709+312A>G intron variant NM_001408413.1:c.706+312A>G intron variant NM_001408414.1:c.709+312A>G intron variant NM_001408415.1:c.709+312A>G intron variant NM_001408416.1:c.706+312A>G intron variant NM_001408418.1:c.670+1414A>G intron variant NM_001408419.1:c.670+1414A>G intron variant NM_001408420.1:c.670+1414A>G intron variant NM_001408421.1:c.667+1414A>G intron variant NM_001408422.1:c.670+1414A>G intron variant NM_001408423.1:c.670+1414A>G intron variant NM_001408424.1:c.667+1414A>G intron variant NM_001408425.1:c.664+312A>G intron variant NM_001408426.1:c.664+312A>G intron variant NM_001408427.1:c.664+312A>G intron variant NM_001408428.1:c.664+312A>G intron variant NM_001408429.1:c.664+312A>G intron variant NM_001408430.1:c.664+312A>G intron variant NM_001408431.1:c.667+1414A>G intron variant NM_001408432.1:c.661+312A>G intron variant NM_001408433.1:c.661+312A>G intron variant NM_001408434.1:c.661+312A>G intron variant NM_001408435.1:c.661+312A>G intron variant NM_001408436.1:c.664+312A>G intron variant NM_001408437.1:c.664+312A>G intron variant NM_001408438.1:c.664+312A>G intron variant NM_001408439.1:c.664+312A>G intron variant NM_001408440.1:c.664+312A>G intron variant NM_001408441.1:c.664+312A>G intron variant NM_001408442.1:c.664+312A>G intron variant NM_001408443.1:c.664+312A>G intron variant NM_001408444.1:c.664+312A>G intron variant NM_001408445.1:c.661+312A>G intron variant NM_001408446.1:c.661+312A>G intron variant NM_001408447.1:c.661+312A>G intron variant NM_001408448.1:c.661+312A>G intron variant NM_001408450.1:c.661+312A>G intron variant NM_001408451.1:c.652+312A>G intron variant NM_001408452.1:c.646+312A>G intron variant NM_001408453.1:c.646+312A>G intron variant NM_001408454.1:c.646+312A>G intron variant NM_001408455.1:c.646+312A>G intron variant NM_001408456.1:c.646+312A>G intron variant NM_001408457.1:c.646+312A>G intron variant NM_001408458.1:c.646+312A>G intron variant NM_001408459.1:c.646+312A>G intron variant NM_001408460.1:c.646+312A>G intron variant NM_001408461.1:c.646+312A>G intron variant NM_001408462.1:c.643+312A>G intron variant NM_001408463.1:c.643+312A>G intron variant NM_001408464.1:c.643+312A>G intron variant NM_001408465.1:c.643+312A>G intron variant NM_001408466.1:c.646+312A>G intron variant NM_001408467.1:c.646+312A>G intron variant NM_001408468.1:c.643+312A>G intron variant NM_001408469.1:c.646+312A>G intron variant NM_001408470.1:c.643+312A>G intron variant NM_001408472.1:c.787+312A>G intron variant NM_001408473.1:c.784+312A>G intron variant NM_001408474.1:c.586+312A>G intron variant NM_001408475.1:c.583+312A>G intron variant NM_001408476.1:c.586+312A>G intron variant NM_001408478.1:c.577+312A>G intron variant NM_001408479.1:c.577+312A>G intron variant NM_001408480.1:c.577+312A>G intron variant NM_001408481.1:c.577+312A>G intron variant NM_001408482.1:c.577+312A>G intron variant NM_001408483.1:c.577+312A>G intron variant NM_001408484.1:c.577+312A>G intron variant NM_001408485.1:c.577+312A>G intron variant NM_001408489.1:c.577+312A>G intron variant NM_001408490.1:c.574+312A>G intron variant NM_001408491.1:c.574+312A>G intron variant NM_001408492.1:c.577+312A>G intron variant NM_001408493.1:c.574+312A>G intron variant NM_001408494.1:c.548-3400A>G intron variant NM_001408495.1:c.545-3400A>G intron variant NM_001408496.1:c.523+312A>G intron variant NM_001408497.1:c.523+312A>G intron variant NM_001408498.1:c.523+312A>G intron variant NM_001408499.1:c.523+312A>G intron variant NM_001408500.1:c.523+312A>G intron variant NM_001408501.1:c.523+312A>G intron variant NM_001408502.1:c.454+312A>G intron variant NM_001408503.1:c.520+312A>G intron variant NM_001408504.1:c.520+312A>G intron variant NM_001408505.1:c.520+312A>G intron variant NM_001408506.1:c.460+1414A>G intron variant NM_001408507.1:c.460+1414A>G intron variant NM_001408508.1:c.451+312A>G intron variant NM_001408509.1:c.451+312A>G intron variant NM_001408510.1:c.406+312A>G intron variant NM_001408511.1:c.404-3400A>G intron variant NM_001408512.1:c.283+312A>G intron variant NM_001408513.1:c.577+312A>G intron variant NM_001408514.1:c.577+312A>G intron variant NM_007297.4:c.958A>G NP_009228.2:p.Thr320Ala missense NM_007298.4:c.787+312A>G intron variant NM_007299.4:c.787+312A>G intron variant NM_007300.4:c.1099A>G NP_009231.2:p.Thr367Ala missense NR_027676.1:n.1235A>G NC_000017.11:g.43094432T>C NC_000017.10:g.41246449T>C NG_005905.2:g.123552A>G LRG_292:g.123552A>G LRG_292t1:c.1099A>G LRG_292p1:p.Thr367Ala - Protein change
- T367A, T320A, T199A, T278A, T239A, T240A, T255A, T296A, T325A, T364A, T366A, T71A, T297A, T299A, T300A, T319A, T326A, T340A, T256A, T279A, T341A
- Other names
- -
- Canonical SPDI
- NC_000017.11:43094431:T:C
-
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 |
13041 | 14847 | |
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
|
Jun 15, 2022 | RCV000228518.15 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Apr 26, 2023 | RCV001177149.9 | |
| Likely benign (1) |
criteria provided, single submitter
|
Feb 9, 2024 | RCV003607272.1 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jul 1, 2024 | RCV004597765.3 |
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
(Jun 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary Breast and Ovarian Cancer
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000403070.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
|
|
|
Uncertain significance
(Jun 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000289736.7
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. 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. ClinVar contains an entry for this variant (Variation ID: 240769). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 367 of the BRCA1 protein (p.Thr367Ala). (less)
|
|
|
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: SCV003846168.1
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).
|
|
|
Uncertain significance
(Apr 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001341310.2
First in ClinVar: Jun 22, 2020 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces threonine with alanine at codon 367 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces threonine with alanine at codon 367 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
|
Likely benign
(Feb 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002580496.2
First in ClinVar: Oct 15, 2022 Last updated: Feb 20, 2024 |
Comment:
ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP
|
|
|
Uncertain significance
(Oct 13, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002732070.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.T367A variant (also known as c.1099A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide … (more)
The p.T367A variant (also known as c.1099A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1099. The threonine at codon 367 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Jul 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV005092420.3
First in ClinVar: Aug 04, 2024 Last updated: Oct 20, 2024 |
Comment:
BRCA1: PM2
Number of individuals with the variant: 1
|
Comment:
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This missense variant replaces threonine with alanine at codon 367 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP
Comment:
The p.T367A variant (also known as c.1099A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1099. The threonine at codon 367 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
BRCA1: PM2
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:
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. 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. ClinVar contains an entry for this variant (Variation ID: 240769). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 367 of the BRCA1 protein (p.Thr367Ala).
Comment:
Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Comment:
This missense variant replaces threonine with alanine at codon 367 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP
Comment:
The p.T367A variant (also known as c.1099A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 1099. The threonine at codon 367 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
BRCA1: PM2
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 rs878854929 ...
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 Nov 03, 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.