The p.Q1408R variant (also known as c.4223A>G), located in coding exon 11 of the BRCA1 gene, results from an A to G substitution at nucleotide position 4223. The glutamine at codon 1408 is replaced by arginine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is 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.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4223A>G (p.Gln1408Arg)
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.
(4)
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
4
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4223A>G (p.Gln1408Arg)
Variation ID: 481440 Accession: VCV000481440.40
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43082538 (GRCh38) [ NCBI UCSC ] 17: 41234555 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 1, 2018 Oct 20, 2024 Sep 1, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4223A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln1408Arg missense NM_001407571.1:c.4010A>G NP_001394500.1:p.Gln1337Arg missense NM_001407581.1:c.4223A>G NP_001394510.1:p.Gln1408Arg missense NM_001407582.1:c.4223A>G NP_001394511.1:p.Gln1408Arg missense NM_001407583.1:c.4223A>G NP_001394512.1:p.Gln1408Arg missense NM_001407585.1:c.4223A>G NP_001394514.1:p.Gln1408Arg missense NM_001407587.1:c.4220A>G NP_001394516.1:p.Gln1407Arg missense NM_001407590.1:c.4220A>G NP_001394519.1:p.Gln1407Arg missense NM_001407591.1:c.4220A>G NP_001394520.1:p.Gln1407Arg missense NM_001407593.1:c.4223A>G NP_001394522.1:p.Gln1408Arg missense NM_001407594.1:c.4223A>G NP_001394523.1:p.Gln1408Arg missense NM_001407596.1:c.4223A>G NP_001394525.1:p.Gln1408Arg missense NM_001407597.1:c.4223A>G NP_001394526.1:p.Gln1408Arg missense NM_001407598.1:c.4223A>G NP_001394527.1:p.Gln1408Arg missense NM_001407602.1:c.4223A>G NP_001394531.1:p.Gln1408Arg missense NM_001407603.1:c.4223A>G NP_001394532.1:p.Gln1408Arg missense NM_001407605.1:c.4223A>G NP_001394534.1:p.Gln1408Arg missense NM_001407610.1:c.4220A>G NP_001394539.1:p.Gln1407Arg missense NM_001407611.1:c.4220A>G NP_001394540.1:p.Gln1407Arg missense NM_001407612.1:c.4220A>G NP_001394541.1:p.Gln1407Arg missense NM_001407613.1:c.4220A>G NP_001394542.1:p.Gln1407Arg missense NM_001407614.1:c.4220A>G NP_001394543.1:p.Gln1407Arg missense NM_001407615.1:c.4220A>G NP_001394544.1:p.Gln1407Arg missense NM_001407616.1:c.4223A>G NP_001394545.1:p.Gln1408Arg missense NM_001407617.1:c.4223A>G NP_001394546.1:p.Gln1408Arg missense NM_001407618.1:c.4223A>G NP_001394547.1:p.Gln1408Arg missense NM_001407619.1:c.4223A>G NP_001394548.1:p.Gln1408Arg missense NM_001407620.1:c.4223A>G NP_001394549.1:p.Gln1408Arg missense NM_001407621.1:c.4223A>G NP_001394550.1:p.Gln1408Arg missense NM_001407622.1:c.4223A>G NP_001394551.1:p.Gln1408Arg missense NM_001407623.1:c.4223A>G NP_001394552.1:p.Gln1408Arg missense NM_001407624.1:c.4220A>G NP_001394553.1:p.Gln1407Arg missense NM_001407625.1:c.4220A>G NP_001394554.1:p.Gln1407Arg missense NM_001407626.1:c.4220A>G NP_001394555.1:p.Gln1407Arg missense NM_001407627.1:c.4217A>G NP_001394556.1:p.Gln1406Arg missense NM_001407628.1:c.4217A>G NP_001394557.1:p.Gln1406Arg missense NM_001407629.1:c.4217A>G NP_001394558.1:p.Gln1406Arg missense NM_001407630.1:c.4217A>G NP_001394559.1:p.Gln1406Arg missense NM_001407631.1:c.4217A>G NP_001394560.1:p.Gln1406Arg missense NM_001407632.1:c.4217A>G NP_001394561.1:p.Gln1406Arg missense NM_001407633.1:c.4220A>G NP_001394562.1:p.Gln1407Arg missense NM_001407634.1:c.4220A>G NP_001394563.1:p.Gln1407Arg missense NM_001407635.1:c.4220A>G NP_001394564.1:p.Gln1407Arg missense NM_001407636.1:c.4220A>G NP_001394565.1:p.Gln1407Arg missense NM_001407637.1:c.4220A>G NP_001394566.1:p.Gln1407Arg missense NM_001407638.1:c.4220A>G NP_001394567.1:p.Gln1407Arg missense NM_001407639.1:c.4220A>G NP_001394568.1:p.Gln1407Arg missense NM_001407640.1:c.4220A>G NP_001394569.1:p.Gln1407Arg missense NM_001407641.1:c.4220A>G NP_001394570.1:p.Gln1407Arg missense NM_001407642.1:c.4220A>G NP_001394571.1:p.Gln1407Arg missense NM_001407644.1:c.4217A>G NP_001394573.1:p.Gln1406Arg missense NM_001407645.1:c.4217A>G NP_001394574.1:p.Gln1406Arg missense NM_001407646.1:c.4211A>G NP_001394575.1:p.Gln1404Arg missense NM_001407647.1:c.4211A>G NP_001394576.1:p.Gln1404Arg missense NM_001407648.1:c.4100A>G NP_001394577.1:p.Gln1367Arg missense NM_001407649.1:c.4097A>G NP_001394578.1:p.Gln1366Arg missense NM_001407652.1:c.4223A>G NP_001394581.1:p.Gln1408Arg missense NM_001407653.1:c.4145A>G NP_001394582.1:p.Gln1382Arg missense NM_001407654.1:c.4145A>G NP_001394583.1:p.Gln1382Arg missense NM_001407655.1:c.4145A>G NP_001394584.1:p.Gln1382Arg missense NM_001407656.1:c.4142A>G NP_001394585.1:p.Gln1381Arg missense NM_001407657.1:c.4145A>G NP_001394586.1:p.Gln1382Arg missense NM_001407658.1:c.4145A>G NP_001394587.1:p.Gln1382Arg missense NM_001407659.1:c.4139A>G NP_001394588.1:p.Gln1380Arg missense NM_001407660.1:c.4139A>G NP_001394589.1:p.Gln1380Arg missense NM_001407661.1:c.4142A>G NP_001394590.1:p.Gln1381Arg missense NM_001407662.1:c.4142A>G NP_001394591.1:p.Gln1381Arg missense NM_001407663.1:c.4142A>G NP_001394592.1:p.Gln1381Arg missense NM_001407664.1:c.4100A>G NP_001394593.1:p.Gln1367Arg missense NM_001407665.1:c.4100A>G NP_001394594.1:p.Gln1367Arg missense NM_001407666.1:c.4100A>G NP_001394595.1:p.Gln1367Arg missense NM_001407667.1:c.4100A>G NP_001394596.1:p.Gln1367Arg missense NM_001407668.1:c.4100A>G NP_001394597.1:p.Gln1367Arg missense NM_001407669.1:c.4100A>G NP_001394598.1:p.Gln1367Arg missense NM_001407670.1:c.4097A>G NP_001394599.1:p.Gln1366Arg missense NM_001407671.1:c.4097A>G NP_001394600.1:p.Gln1366Arg missense NM_001407672.1:c.4097A>G NP_001394601.1:p.Gln1366Arg missense NM_001407673.1:c.4097A>G NP_001394602.1:p.Gln1366Arg missense NM_001407674.1:c.4097A>G NP_001394603.1:p.Gln1366Arg missense NM_001407675.1:c.4097A>G NP_001394604.1:p.Gln1366Arg missense NM_001407676.1:c.4097A>G NP_001394605.1:p.Gln1366Arg missense NM_001407677.1:c.4100A>G NP_001394606.1:p.Gln1367Arg missense NM_001407678.1:c.4100A>G NP_001394607.1:p.Gln1367Arg missense NM_001407679.1:c.4100A>G NP_001394608.1:p.Gln1367Arg missense NM_001407680.1:c.4100A>G NP_001394609.1:p.Gln1367Arg missense NM_001407681.1:c.4097A>G NP_001394610.1:p.Gln1366Arg missense NM_001407682.1:c.4097A>G NP_001394611.1:p.Gln1366Arg missense NM_001407683.1:c.4097A>G NP_001394612.1:p.Gln1366Arg missense NM_001407684.1:c.4223A>G NP_001394613.1:p.Gln1408Arg missense NM_001407685.1:c.4094A>G NP_001394614.1:p.Gln1365Arg missense NM_001407686.1:c.4094A>G NP_001394615.1:p.Gln1365Arg missense NM_001407687.1:c.4094A>G NP_001394616.1:p.Gln1365Arg missense NM_001407688.1:c.4097A>G NP_001394617.1:p.Gln1366Arg missense NM_001407689.1:c.4097A>G NP_001394618.1:p.Gln1366Arg missense NM_001407690.1:c.4094A>G NP_001394619.1:p.Gln1365Arg missense NM_001407691.1:c.4094A>G NP_001394620.1:p.Gln1365Arg missense NM_001407692.1:c.4082A>G NP_001394621.1:p.Gln1361Arg missense NM_001407694.1:c.4082A>G NP_001394623.1:p.Gln1361Arg missense NM_001407695.1:c.4082A>G NP_001394624.1:p.Gln1361Arg missense NM_001407696.1:c.4082A>G NP_001394625.1:p.Gln1361Arg missense NM_001407697.1:c.4082A>G NP_001394626.1:p.Gln1361Arg missense NM_001407698.1:c.4082A>G NP_001394627.1:p.Gln1361Arg missense NM_001407724.1:c.4082A>G NP_001394653.1:p.Gln1361Arg missense NM_001407725.1:c.4082A>G NP_001394654.1:p.Gln1361Arg missense NM_001407726.1:c.4082A>G NP_001394655.1:p.Gln1361Arg missense NM_001407727.1:c.4082A>G NP_001394656.1:p.Gln1361Arg missense NM_001407728.1:c.4082A>G NP_001394657.1:p.Gln1361Arg missense NM_001407729.1:c.4082A>G NP_001394658.1:p.Gln1361Arg missense NM_001407730.1:c.4082A>G NP_001394659.1:p.Gln1361Arg missense NM_001407731.1:c.4082A>G NP_001394660.1:p.Gln1361Arg missense NM_001407732.1:c.4082A>G NP_001394661.1:p.Gln1361Arg missense NM_001407733.1:c.4082A>G NP_001394662.1:p.Gln1361Arg missense NM_001407734.1:c.4082A>G NP_001394663.1:p.Gln1361Arg missense NM_001407735.1:c.4082A>G NP_001394664.1:p.Gln1361Arg missense NM_001407736.1:c.4082A>G NP_001394665.1:p.Gln1361Arg missense NM_001407737.1:c.4082A>G NP_001394666.1:p.Gln1361Arg missense NM_001407738.1:c.4082A>G NP_001394667.1:p.Gln1361Arg missense NM_001407739.1:c.4082A>G NP_001394668.1:p.Gln1361Arg missense NM_001407740.1:c.4079A>G NP_001394669.1:p.Gln1360Arg missense NM_001407741.1:c.4079A>G NP_001394670.1:p.Gln1360Arg missense NM_001407742.1:c.4079A>G NP_001394671.1:p.Gln1360Arg missense NM_001407743.1:c.4079A>G NP_001394672.1:p.Gln1360Arg missense NM_001407744.1:c.4079A>G NP_001394673.1:p.Gln1360Arg missense NM_001407745.1:c.4079A>G NP_001394674.1:p.Gln1360Arg missense NM_001407746.1:c.4079A>G NP_001394675.1:p.Gln1360Arg missense NM_001407747.1:c.4079A>G NP_001394676.1:p.Gln1360Arg missense NM_001407748.1:c.4079A>G NP_001394677.1:p.Gln1360Arg missense NM_001407749.1:c.4079A>G NP_001394678.1:p.Gln1360Arg missense NM_001407750.1:c.4079A>G NP_001394679.1:p.Gln1360Arg missense NM_001407751.1:c.4079A>G NP_001394680.1:p.Gln1360Arg missense NM_001407752.1:c.4079A>G NP_001394681.1:p.Gln1360Arg missense NM_001407838.1:c.4079A>G NP_001394767.1:p.Gln1360Arg missense NM_001407839.1:c.4079A>G NP_001394768.1:p.Gln1360Arg missense NM_001407841.1:c.4079A>G NP_001394770.1:p.Gln1360Arg missense NM_001407842.1:c.4079A>G NP_001394771.1:p.Gln1360Arg missense NM_001407843.1:c.4079A>G NP_001394772.1:p.Gln1360Arg missense NM_001407844.1:c.4079A>G NP_001394773.1:p.Gln1360Arg missense NM_001407845.1:c.4079A>G NP_001394774.1:p.Gln1360Arg missense NM_001407846.1:c.4079A>G NP_001394775.1:p.Gln1360Arg missense NM_001407847.1:c.4076A>G NP_001394776.1:p.Gln1359Arg missense NM_001407848.1:c.4076A>G NP_001394777.1:p.Gln1359Arg missense NM_001407849.1:c.4076A>G NP_001394778.1:p.Gln1359Arg missense NM_001407850.1:c.4079A>G NP_001394779.1:p.Gln1360Arg missense NM_001407851.1:c.4079A>G NP_001394780.1:p.Gln1360Arg missense NM_001407852.1:c.4079A>G NP_001394781.1:p.Gln1360Arg missense NM_001407853.1:c.4010A>G NP_001394782.1:p.Gln1337Arg missense NM_001407854.1:c.4223A>G NP_001394783.1:p.Gln1408Arg missense NM_001407858.1:c.4223A>G NP_001394787.1:p.Gln1408Arg missense NM_001407859.1:c.4223A>G NP_001394788.1:p.Gln1408Arg missense NM_001407860.1:c.4220A>G NP_001394789.1:p.Gln1407Arg missense NM_001407861.1:c.4220A>G NP_001394790.1:p.Gln1407Arg missense NM_001407862.1:c.4022A>G NP_001394791.1:p.Gln1341Arg missense NM_001407863.1:c.4100A>G NP_001394792.1:p.Gln1367Arg missense NM_001407874.1:c.4019A>G NP_001394803.1:p.Gln1340Arg missense NM_001407875.1:c.4019A>G NP_001394804.1:p.Gln1340Arg missense NM_001407879.1:c.4013A>G NP_001394808.1:p.Gln1338Arg missense NM_001407881.1:c.4013A>G NP_001394810.1:p.Gln1338Arg missense NM_001407882.1:c.4013A>G NP_001394811.1:p.Gln1338Arg missense NM_001407884.1:c.4013A>G NP_001394813.1:p.Gln1338Arg missense NM_001407885.1:c.4013A>G NP_001394814.1:p.Gln1338Arg missense NM_001407886.1:c.4013A>G NP_001394815.1:p.Gln1338Arg missense NM_001407887.1:c.4013A>G NP_001394816.1:p.Gln1338Arg missense NM_001407889.1:c.4013A>G NP_001394818.1:p.Gln1338Arg missense NM_001407894.1:c.4010A>G NP_001394823.1:p.Gln1337Arg missense NM_001407895.1:c.4010A>G NP_001394824.1:p.Gln1337Arg missense NM_001407896.1:c.4010A>G NP_001394825.1:p.Gln1337Arg missense NM_001407897.1:c.4010A>G NP_001394826.1:p.Gln1337Arg missense NM_001407898.1:c.4010A>G NP_001394827.1:p.Gln1337Arg missense NM_001407899.1:c.4010A>G NP_001394828.1:p.Gln1337Arg missense NM_001407900.1:c.4013A>G NP_001394829.1:p.Gln1338Arg missense NM_001407902.1:c.4013A>G NP_001394831.1:p.Gln1338Arg missense NM_001407904.1:c.4013A>G NP_001394833.1:p.Gln1338Arg missense NM_001407906.1:c.4013A>G NP_001394835.1:p.Gln1338Arg missense NM_001407907.1:c.4010A>G NP_001394836.1:p.Gln1337Arg missense NM_001407908.1:c.4010A>G NP_001394837.1:p.Gln1337Arg missense NM_001407909.1:c.4010A>G NP_001394838.1:p.Gln1337Arg missense NM_001407910.1:c.4010A>G NP_001394839.1:p.Gln1337Arg missense NM_001407915.1:c.4007A>G NP_001394844.1:p.Gln1336Arg missense NM_001407916.1:c.4010A>G NP_001394845.1:p.Gln1337Arg missense NM_001407917.1:c.4010A>G NP_001394846.1:p.Gln1337Arg missense NM_001407918.1:c.4010A>G NP_001394847.1:p.Gln1337Arg missense NM_001407919.1:c.4100A>G NP_001394848.1:p.Gln1367Arg missense NM_001407920.1:c.3959A>G NP_001394849.1:p.Gln1320Arg missense NM_001407921.1:c.3959A>G NP_001394850.1:p.Gln1320Arg missense NM_001407922.1:c.3959A>G NP_001394851.1:p.Gln1320Arg missense NM_001407923.1:c.3959A>G NP_001394852.1:p.Gln1320Arg missense NM_001407924.1:c.3959A>G NP_001394853.1:p.Gln1320Arg missense NM_001407925.1:c.3959A>G NP_001394854.1:p.Gln1320Arg missense NM_001407926.1:c.3959A>G NP_001394855.1:p.Gln1320Arg missense NM_001407927.1:c.3959A>G NP_001394856.1:p.Gln1320Arg missense NM_001407928.1:c.3959A>G NP_001394857.1:p.Gln1320Arg missense NM_001407929.1:c.3959A>G NP_001394858.1:p.Gln1320Arg missense NM_001407930.1:c.3956A>G NP_001394859.1:p.Gln1319Arg missense NM_001407931.1:c.3956A>G NP_001394860.1:p.Gln1319Arg missense NM_001407932.1:c.3956A>G NP_001394861.1:p.Gln1319Arg missense NM_001407933.1:c.3956A>G NP_001394862.1:p.Gln1319Arg missense NM_001407934.1:c.3953A>G NP_001394863.1:p.Gln1318Arg missense NM_001407935.1:c.3956A>G NP_001394864.1:p.Gln1319Arg missense NM_001407936.1:c.3956A>G NP_001394865.1:p.Gln1319Arg missense NM_001407937.1:c.4100A>G NP_001394866.1:p.Gln1367Arg missense NM_001407938.1:c.4100A>G NP_001394867.1:p.Gln1367Arg missense NM_001407939.1:c.4100A>G NP_001394868.1:p.Gln1367Arg missense NM_001407940.1:c.4097A>G NP_001394869.1:p.Gln1366Arg missense NM_001407941.1:c.4097A>G NP_001394870.1:p.Gln1366Arg missense NM_001407942.1:c.4082A>G NP_001394871.1:p.Gln1361Arg missense NM_001407943.1:c.4079A>G NP_001394872.1:p.Gln1360Arg missense NM_001407944.1:c.4082A>G NP_001394873.1:p.Gln1361Arg missense NM_001407945.1:c.4082A>G NP_001394874.1:p.Gln1361Arg missense NM_001407946.1:c.3890A>G NP_001394875.1:p.Gln1297Arg missense NM_001407947.1:c.3890A>G NP_001394876.1:p.Gln1297Arg missense NM_001407948.1:c.3890A>G NP_001394877.1:p.Gln1297Arg missense NM_001407949.1:c.3890A>G NP_001394878.1:p.Gln1297Arg missense NM_001407950.1:c.3890A>G NP_001394879.1:p.Gln1297Arg missense NM_001407951.1:c.3890A>G NP_001394880.1:p.Gln1297Arg missense NM_001407952.1:c.3887A>G NP_001394881.1:p.Gln1296Arg missense NM_001407953.1:c.3887A>G NP_001394882.1:p.Gln1296Arg missense NM_001407954.1:c.3887A>G NP_001394883.1:p.Gln1296Arg missense NM_001407955.1:c.3887A>G NP_001394884.1:p.Gln1296Arg missense NM_001407956.1:c.3884A>G NP_001394885.1:p.Gln1295Arg missense NM_001407957.1:c.3887A>G NP_001394886.1:p.Gln1296Arg missense NM_001407958.1:c.3887A>G NP_001394887.1:p.Gln1296Arg missense NM_001407959.1:c.3842A>G NP_001394888.1:p.Gln1281Arg missense NM_001407960.1:c.3842A>G NP_001394889.1:p.Gln1281Arg missense NM_001407962.1:c.3839A>G NP_001394891.1:p.Gln1280Arg missense NM_001407963.1:c.3839A>G NP_001394892.1:p.Gln1280Arg missense NM_001407964.1:c.4079A>G NP_001394893.1:p.Gln1360Arg missense NM_001407965.1:c.3716A>G NP_001394894.1:p.Gln1239Arg missense NM_001407966.1:c.3335A>G NP_001394895.1:p.Gln1112Arg missense NM_001407967.1:c.3335A>G NP_001394896.1:p.Gln1112Arg missense NM_001407968.1:c.1619A>G NP_001394897.1:p.Gln540Arg missense NM_001407969.1:c.1616A>G NP_001394898.1:p.Gln539Arg missense NM_001407970.1:c.914A>G NP_001394899.1:p.Gln305Arg missense NM_001407971.1:c.914A>G NP_001394900.1:p.Gln305Arg missense NM_001407972.1:c.911A>G NP_001394901.1:p.Gln304Arg missense NM_001407973.1:c.914A>G NP_001394902.1:p.Gln305Arg missense NM_001407974.1:c.914A>G NP_001394903.1:p.Gln305Arg missense NM_001407975.1:c.914A>G NP_001394904.1:p.Gln305Arg missense NM_001407976.1:c.914A>G NP_001394905.1:p.Gln305Arg missense NM_001407977.1:c.914A>G NP_001394906.1:p.Gln305Arg missense NM_001407978.1:c.914A>G NP_001394907.1:p.Gln305Arg missense NM_001407979.1:c.911A>G NP_001394908.1:p.Gln304Arg missense NM_001407980.1:c.911A>G NP_001394909.1:p.Gln304Arg missense NM_001407981.1:c.911A>G NP_001394910.1:p.Gln304Arg missense NM_001407982.1:c.911A>G NP_001394911.1:p.Gln304Arg missense NM_001407983.1:c.911A>G NP_001394912.1:p.Gln304Arg missense NM_001407984.1:c.911A>G NP_001394913.1:p.Gln304Arg missense NM_001407985.1:c.911A>G NP_001394914.1:p.Gln304Arg missense NM_001407986.1:c.911A>G NP_001394915.1:p.Gln304Arg missense NM_001407990.1:c.911A>G NP_001394919.1:p.Gln304Arg missense NM_001407991.1:c.911A>G NP_001394920.1:p.Gln304Arg missense NM_001407992.1:c.911A>G NP_001394921.1:p.Gln304Arg missense NM_001407993.1:c.914A>G NP_001394922.1:p.Gln305Arg missense NM_001408392.1:c.911A>G NP_001395321.1:p.Gln304Arg missense NM_001408396.1:c.911A>G NP_001395325.1:p.Gln304Arg missense NM_001408397.1:c.911A>G NP_001395326.1:p.Gln304Arg missense NM_001408398.1:c.911A>G NP_001395327.1:p.Gln304Arg missense NM_001408399.1:c.911A>G NP_001395328.1:p.Gln304Arg missense NM_001408400.1:c.908A>G NP_001395329.1:p.Gln303Arg missense NM_001408401.1:c.908A>G NP_001395330.1:p.Gln303Arg missense NM_001408402.1:c.908A>G NP_001395331.1:p.Gln303Arg missense NM_001408403.1:c.911A>G NP_001395332.1:p.Gln304Arg missense NM_001408404.1:c.911A>G NP_001395333.1:p.Gln304Arg missense NM_001408406.1:c.905A>G NP_001395335.1:p.Gln302Arg missense NM_001408407.1:c.908A>G NP_001395336.1:p.Gln303Arg missense NM_001408408.1:c.905A>G NP_001395337.1:p.Gln302Arg missense NM_001408409.1:c.836A>G NP_001395338.1:p.Gln279Arg missense NM_001408410.1:c.773A>G NP_001395339.1:p.Gln258Arg missense NM_001408411.1:c.836A>G NP_001395340.1:p.Gln279Arg missense NM_001408412.1:c.836A>G NP_001395341.1:p.Gln279Arg missense NM_001408413.1:c.833A>G NP_001395342.1:p.Gln278Arg missense NM_001408414.1:c.836A>G NP_001395343.1:p.Gln279Arg missense NM_001408415.1:c.836A>G NP_001395344.1:p.Gln279Arg missense NM_001408416.1:c.833A>G NP_001395345.1:p.Gln278Arg missense NM_001408418.1:c.797A>G NP_001395347.1:p.Gln266Arg missense NM_001408419.1:c.797A>G NP_001395348.1:p.Gln266Arg missense NM_001408420.1:c.797A>G NP_001395349.1:p.Gln266Arg missense NM_001408421.1:c.794A>G NP_001395350.1:p.Gln265Arg missense NM_001408422.1:c.797A>G NP_001395351.1:p.Gln266Arg missense NM_001408423.1:c.797A>G NP_001395352.1:p.Gln266Arg missense NM_001408424.1:c.794A>G NP_001395353.1:p.Gln265Arg missense NM_001408425.1:c.791A>G NP_001395354.1:p.Gln264Arg missense NM_001408426.1:c.791A>G NP_001395355.1:p.Gln264Arg missense NM_001408427.1:c.791A>G NP_001395356.1:p.Gln264Arg missense NM_001408428.1:c.791A>G NP_001395357.1:p.Gln264Arg missense NM_001408429.1:c.791A>G NP_001395358.1:p.Gln264Arg missense NM_001408430.1:c.791A>G NP_001395359.1:p.Gln264Arg missense NM_001408431.1:c.794A>G NP_001395360.1:p.Gln265Arg missense NM_001408432.1:c.788A>G NP_001395361.1:p.Gln263Arg missense NM_001408433.1:c.788A>G NP_001395362.1:p.Gln263Arg missense NM_001408434.1:c.788A>G NP_001395363.1:p.Gln263Arg missense NM_001408435.1:c.788A>G NP_001395364.1:p.Gln263Arg missense NM_001408436.1:c.791A>G NP_001395365.1:p.Gln264Arg missense NM_001408437.1:c.791A>G NP_001395366.1:p.Gln264Arg missense NM_001408438.1:c.791A>G NP_001395367.1:p.Gln264Arg missense NM_001408439.1:c.791A>G NP_001395368.1:p.Gln264Arg missense NM_001408440.1:c.791A>G NP_001395369.1:p.Gln264Arg missense NM_001408441.1:c.788A>G NP_001395370.1:p.Gln263Arg missense NM_001408442.1:c.788A>G NP_001395371.1:p.Gln263Arg missense NM_001408443.1:c.788A>G NP_001395372.1:p.Gln263Arg missense NM_001408444.1:c.788A>G NP_001395373.1:p.Gln263Arg missense NM_001408445.1:c.788A>G NP_001395374.1:p.Gln263Arg missense NM_001408446.1:c.788A>G NP_001395375.1:p.Gln263Arg missense NM_001408447.1:c.788A>G NP_001395376.1:p.Gln263Arg missense NM_001408448.1:c.788A>G NP_001395377.1:p.Gln263Arg missense NM_001408450.1:c.788A>G NP_001395379.1:p.Gln263Arg missense NM_001408451.1:c.779A>G NP_001395380.1:p.Gln260Arg missense NM_001408452.1:c.773A>G NP_001395381.1:p.Gln258Arg missense NM_001408453.1:c.773A>G NP_001395382.1:p.Gln258Arg missense NM_001408454.1:c.773A>G NP_001395383.1:p.Gln258Arg missense NM_001408455.1:c.773A>G NP_001395384.1:p.Gln258Arg missense NM_001408456.1:c.773A>G NP_001395385.1:p.Gln258Arg missense NM_001408457.1:c.773A>G NP_001395386.1:p.Gln258Arg missense NM_001408458.1:c.773A>G NP_001395387.1:p.Gln258Arg missense NM_001408459.1:c.773A>G NP_001395388.1:p.Gln258Arg missense NM_001408460.1:c.773A>G NP_001395389.1:p.Gln258Arg missense NM_001408461.1:c.773A>G NP_001395390.1:p.Gln258Arg missense NM_001408462.1:c.770A>G NP_001395391.1:p.Gln257Arg missense NM_001408463.1:c.770A>G NP_001395392.1:p.Gln257Arg missense NM_001408464.1:c.770A>G NP_001395393.1:p.Gln257Arg missense NM_001408465.1:c.770A>G NP_001395394.1:p.Gln257Arg missense NM_001408466.1:c.770A>G NP_001395395.1:p.Gln257Arg missense NM_001408467.1:c.770A>G NP_001395396.1:p.Gln257Arg missense NM_001408468.1:c.770A>G NP_001395397.1:p.Gln257Arg missense NM_001408469.1:c.770A>G NP_001395398.1:p.Gln257Arg missense NM_001408470.1:c.767A>G NP_001395399.1:p.Gln256Arg missense NM_001408472.1:c.911A>G NP_001395401.1:p.Gln304Arg missense NM_001408473.1:c.911A>G NP_001395402.1:p.Gln304Arg missense NM_001408474.1:c.713A>G NP_001395403.1:p.Gln238Arg missense NM_001408475.1:c.710A>G NP_001395404.1:p.Gln237Arg missense NM_001408476.1:c.713A>G NP_001395405.1:p.Gln238Arg missense NM_001408478.1:c.704A>G NP_001395407.1:p.Gln235Arg missense NM_001408479.1:c.704A>G NP_001395408.1:p.Gln235Arg missense NM_001408480.1:c.704A>G NP_001395409.1:p.Gln235Arg missense NM_001408481.1:c.704A>G NP_001395410.1:p.Gln235Arg missense NM_001408482.1:c.704A>G NP_001395411.1:p.Gln235Arg missense NM_001408483.1:c.704A>G NP_001395412.1:p.Gln235Arg missense NM_001408484.1:c.704A>G NP_001395413.1:p.Gln235Arg missense NM_001408485.1:c.704A>G NP_001395414.1:p.Gln235Arg missense NM_001408489.1:c.701A>G NP_001395418.1:p.Gln234Arg missense NM_001408490.1:c.701A>G NP_001395419.1:p.Gln234Arg missense NM_001408491.1:c.701A>G NP_001395420.1:p.Gln234Arg missense NM_001408492.1:c.701A>G NP_001395421.1:p.Gln234Arg missense NM_001408493.1:c.701A>G NP_001395422.1:p.Gln234Arg missense NM_001408494.1:c.674A>G NP_001395423.1:p.Gln225Arg missense NM_001408495.1:c.671A>G NP_001395424.1:p.Gln224Arg missense NM_001408496.1:c.650A>G NP_001395425.1:p.Gln217Arg missense NM_001408497.1:c.650A>G NP_001395426.1:p.Gln217Arg missense NM_001408498.1:c.650A>G NP_001395427.1:p.Gln217Arg missense NM_001408499.1:c.650A>G NP_001395428.1:p.Gln217Arg missense NM_001408500.1:c.650A>G NP_001395429.1:p.Gln217Arg missense NM_001408501.1:c.650A>G NP_001395430.1:p.Gln217Arg missense NM_001408502.1:c.581A>G NP_001395431.1:p.Gln194Arg missense NM_001408503.1:c.647A>G NP_001395432.1:p.Gln216Arg missense NM_001408504.1:c.647A>G NP_001395433.1:p.Gln216Arg missense NM_001408505.1:c.647A>G NP_001395434.1:p.Gln216Arg missense NM_001408506.1:c.587A>G NP_001395435.1:p.Gln196Arg missense NM_001408507.1:c.584A>G NP_001395436.1:p.Gln195Arg missense NM_001408508.1:c.575A>G NP_001395437.1:p.Gln192Arg missense NM_001408509.1:c.575A>G NP_001395438.1:p.Gln192Arg missense NM_001408510.1:c.533A>G NP_001395439.1:p.Gln178Arg missense NM_001408511.1:c.530A>G NP_001395440.1:p.Gln177Arg missense NM_001408512.1:c.410A>G NP_001395441.1:p.Gln137Arg missense NM_001408513.1:c.701A>G NP_001395442.1:p.Gln234Arg missense NM_001408514.1:c.704A>G NP_001395443.1:p.Gln235Arg missense NM_007297.4:c.4082A>G NP_009228.2:p.Gln1361Arg missense NM_007298.4:c.914A>G NP_009229.2:p.Gln305Arg missense NM_007299.4:c.914A>G NP_009230.2:p.Gln305Arg missense NM_007300.4:c.4223A>G NP_009231.2:p.Gln1408Arg missense NM_007304.2:c.914A>G NP_009235.2:p.Gln305Arg missense NR_027676.2:n.4400A>G non-coding transcript variant NC_000017.11:g.43082538T>C NC_000017.10:g.41234555T>C NG_005905.2:g.135446A>G LRG_292:g.135446A>G LRG_292t1:c.4223A>G LRG_292p1:p.Gln1408Arg - Protein change
- Q1408R, Q1361R, Q305R, Q1112R, Q1296R, Q1319R, Q1337R, Q1338R, Q1341R, Q1359R, Q1366R, Q137R, Q1406R, Q177R, Q196R, Q224R, Q260R, Q265R, Q1239R, Q1297R, Q1360R, Q1367R, Q1381R, Q1382R, Q178R, Q192R, Q194R, Q195R, Q237R, Q257R, Q263R, Q302R, Q303R, Q539R, Q540R, Q238R, Q266R, Q279R, Q304R, Q1280R, Q1295R, Q1320R, Q1336R, Q1340R, Q1365R, Q216R, Q217R, Q234R, Q235R, Q1281R, Q1318R, Q1380R, Q1404R, Q1407R, Q225R, Q256R, Q258R, Q264R, Q278R
- Other names
- -
- Canonical SPDI
- NC_000017.11:43082537: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 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 1, 2023 | RCV000567083.6 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Oct 31, 2022 | RCV001362725.9 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Apr 1, 2020 | RCV001171795.23 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Sep 1, 2023 | RCV003483673.1 |
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
(Sep 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000665837.6
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The p.Q1408R variant (also known as c.4223A>G), located in coding exon 11 of the BRCA1 gene, results from an A to G substitution at nucleotide … (more)
The p.Q1408R variant (also known as c.4223A>G), located in coding exon 11 of the BRCA1 gene, results from an A to G substitution at nucleotide position 4223. The glutamine at codon 1408 is replaced by arginine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is 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
(Oct 31, 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: SCV001558757.4
First in ClinVar: Apr 13, 2021 Last updated: Feb 28, 2024 |
Comment:
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) … (more)
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: 481440). This missense change has been observed in individual(s) with breast cancer (PMID: 30254663). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1408 of the BRCA1 protein (p.Gln1408Arg). 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
(Apr 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001334653.25
First in ClinVar: Jun 08, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Uncertain significance
(Sep 01, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical and Surgical Sciences, University of Bologna
Accession: SCV004228358.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
PM2(Supporting)+BP4(Supporting) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
|
Comment:
Comment:
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: 481440). This missense change has been observed in individual(s) with breast cancer (PMID: 30254663). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1408 of the BRCA1 protein (p.Gln1408Arg). 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:
PM2(Supporting)+BP4(Supporting) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
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:
The p.Q1408R variant (also known as c.4223A>G), located in coding exon 11 of the BRCA1 gene, results from an A to G substitution at nucleotide position 4223. The glutamine at codon 1408 is replaced by arginine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is 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:
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: 481440). This missense change has been observed in individual(s) with breast cancer (PMID: 30254663). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1408 of the BRCA1 protein (p.Gln1408Arg). 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:
PM2(Supporting)+BP4(Supporting) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help? | Zuntini R | Frontiers in genetics | 2018 | PMID: 30254663 |
Text-mined citations for rs1555584227 ...
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 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.