This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1423 of the BRCA1 protein (p.Ser1423Asn). 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: 946942). 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%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4268G>A (p.Ser1423Asn)
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.4268G>A (p.Ser1423Asn)
Variation ID: 946942 Accession: VCV000946942.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43082493 (GRCh38) [ NCBI UCSC ] 17: 41234510 (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 16, 2020 Oct 8, 2024 Jan 17, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4268G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ser1423Asn missense NM_001407571.1:c.4055G>A NP_001394500.1:p.Ser1352Asn missense NM_001407581.1:c.4268G>A NP_001394510.1:p.Ser1423Asn missense NM_001407582.1:c.4268G>A NP_001394511.1:p.Ser1423Asn missense NM_001407583.1:c.4268G>A NP_001394512.1:p.Ser1423Asn missense NM_001407585.1:c.4268G>A NP_001394514.1:p.Ser1423Asn missense NM_001407587.1:c.4265G>A NP_001394516.1:p.Ser1422Asn missense NM_001407590.1:c.4265G>A NP_001394519.1:p.Ser1422Asn missense NM_001407591.1:c.4265G>A NP_001394520.1:p.Ser1422Asn missense NM_001407593.1:c.4268G>A NP_001394522.1:p.Ser1423Asn missense NM_001407594.1:c.4268G>A NP_001394523.1:p.Ser1423Asn missense NM_001407596.1:c.4268G>A NP_001394525.1:p.Ser1423Asn missense NM_001407597.1:c.4268G>A NP_001394526.1:p.Ser1423Asn missense NM_001407598.1:c.4268G>A NP_001394527.1:p.Ser1423Asn missense NM_001407602.1:c.4268G>A NP_001394531.1:p.Ser1423Asn missense NM_001407603.1:c.4268G>A NP_001394532.1:p.Ser1423Asn missense NM_001407605.1:c.4268G>A NP_001394534.1:p.Ser1423Asn missense NM_001407610.1:c.4265G>A NP_001394539.1:p.Ser1422Asn missense NM_001407611.1:c.4265G>A NP_001394540.1:p.Ser1422Asn missense NM_001407612.1:c.4265G>A NP_001394541.1:p.Ser1422Asn missense NM_001407613.1:c.4265G>A NP_001394542.1:p.Ser1422Asn missense NM_001407614.1:c.4265G>A NP_001394543.1:p.Ser1422Asn missense NM_001407615.1:c.4265G>A NP_001394544.1:p.Ser1422Asn missense NM_001407616.1:c.4268G>A NP_001394545.1:p.Ser1423Asn missense NM_001407617.1:c.4268G>A NP_001394546.1:p.Ser1423Asn missense NM_001407618.1:c.4268G>A NP_001394547.1:p.Ser1423Asn missense NM_001407619.1:c.4268G>A NP_001394548.1:p.Ser1423Asn missense NM_001407620.1:c.4268G>A NP_001394549.1:p.Ser1423Asn missense NM_001407621.1:c.4268G>A NP_001394550.1:p.Ser1423Asn missense NM_001407622.1:c.4268G>A NP_001394551.1:p.Ser1423Asn missense NM_001407623.1:c.4268G>A NP_001394552.1:p.Ser1423Asn missense NM_001407624.1:c.4265G>A NP_001394553.1:p.Ser1422Asn missense NM_001407625.1:c.4265G>A NP_001394554.1:p.Ser1422Asn missense NM_001407626.1:c.4265G>A NP_001394555.1:p.Ser1422Asn missense NM_001407627.1:c.4262G>A NP_001394556.1:p.Ser1421Asn missense NM_001407628.1:c.4262G>A NP_001394557.1:p.Ser1421Asn missense NM_001407629.1:c.4262G>A NP_001394558.1:p.Ser1421Asn missense NM_001407630.1:c.4262G>A NP_001394559.1:p.Ser1421Asn missense NM_001407631.1:c.4262G>A NP_001394560.1:p.Ser1421Asn missense NM_001407632.1:c.4262G>A NP_001394561.1:p.Ser1421Asn missense NM_001407633.1:c.4265G>A NP_001394562.1:p.Ser1422Asn missense NM_001407634.1:c.4265G>A NP_001394563.1:p.Ser1422Asn missense NM_001407635.1:c.4265G>A NP_001394564.1:p.Ser1422Asn missense NM_001407636.1:c.4265G>A NP_001394565.1:p.Ser1422Asn missense NM_001407637.1:c.4265G>A NP_001394566.1:p.Ser1422Asn missense NM_001407638.1:c.4265G>A NP_001394567.1:p.Ser1422Asn missense NM_001407639.1:c.4265G>A NP_001394568.1:p.Ser1422Asn missense NM_001407640.1:c.4265G>A NP_001394569.1:p.Ser1422Asn missense NM_001407641.1:c.4265G>A NP_001394570.1:p.Ser1422Asn missense NM_001407642.1:c.4265G>A NP_001394571.1:p.Ser1422Asn missense NM_001407644.1:c.4262G>A NP_001394573.1:p.Ser1421Asn missense NM_001407645.1:c.4262G>A NP_001394574.1:p.Ser1421Asn missense NM_001407646.1:c.4256G>A NP_001394575.1:p.Ser1419Asn missense NM_001407647.1:c.4256G>A NP_001394576.1:p.Ser1419Asn missense NM_001407648.1:c.4145G>A NP_001394577.1:p.Ser1382Asn missense NM_001407649.1:c.4142G>A NP_001394578.1:p.Ser1381Asn missense NM_001407652.1:c.4268G>A NP_001394581.1:p.Ser1423Asn missense NM_001407653.1:c.4190G>A NP_001394582.1:p.Ser1397Asn missense NM_001407654.1:c.4190G>A NP_001394583.1:p.Ser1397Asn missense NM_001407655.1:c.4190G>A NP_001394584.1:p.Ser1397Asn missense NM_001407656.1:c.4187G>A NP_001394585.1:p.Ser1396Asn missense NM_001407657.1:c.4190G>A NP_001394586.1:p.Ser1397Asn missense NM_001407658.1:c.4190G>A NP_001394587.1:p.Ser1397Asn missense NM_001407659.1:c.4184G>A NP_001394588.1:p.Ser1395Asn missense NM_001407660.1:c.4184G>A NP_001394589.1:p.Ser1395Asn missense NM_001407661.1:c.4187G>A NP_001394590.1:p.Ser1396Asn missense NM_001407662.1:c.4187G>A NP_001394591.1:p.Ser1396Asn missense NM_001407663.1:c.4187G>A NP_001394592.1:p.Ser1396Asn missense NM_001407664.1:c.4145G>A NP_001394593.1:p.Ser1382Asn missense NM_001407665.1:c.4145G>A NP_001394594.1:p.Ser1382Asn missense NM_001407666.1:c.4145G>A NP_001394595.1:p.Ser1382Asn missense NM_001407667.1:c.4145G>A NP_001394596.1:p.Ser1382Asn missense NM_001407668.1:c.4145G>A NP_001394597.1:p.Ser1382Asn missense NM_001407669.1:c.4145G>A NP_001394598.1:p.Ser1382Asn missense NM_001407670.1:c.4142G>A NP_001394599.1:p.Ser1381Asn missense NM_001407671.1:c.4142G>A NP_001394600.1:p.Ser1381Asn missense NM_001407672.1:c.4142G>A NP_001394601.1:p.Ser1381Asn missense NM_001407673.1:c.4142G>A NP_001394602.1:p.Ser1381Asn missense NM_001407674.1:c.4142G>A NP_001394603.1:p.Ser1381Asn missense NM_001407675.1:c.4142G>A NP_001394604.1:p.Ser1381Asn missense NM_001407676.1:c.4142G>A NP_001394605.1:p.Ser1381Asn missense NM_001407677.1:c.4145G>A NP_001394606.1:p.Ser1382Asn missense NM_001407678.1:c.4145G>A NP_001394607.1:p.Ser1382Asn missense NM_001407679.1:c.4145G>A NP_001394608.1:p.Ser1382Asn missense NM_001407680.1:c.4145G>A NP_001394609.1:p.Ser1382Asn missense NM_001407681.1:c.4142G>A NP_001394610.1:p.Ser1381Asn missense NM_001407682.1:c.4142G>A NP_001394611.1:p.Ser1381Asn missense NM_001407683.1:c.4142G>A NP_001394612.1:p.Ser1381Asn missense NM_001407684.1:c.4268G>A NP_001394613.1:p.Ser1423Asn missense NM_001407685.1:c.4139G>A NP_001394614.1:p.Ser1380Asn missense NM_001407686.1:c.4139G>A NP_001394615.1:p.Ser1380Asn missense NM_001407687.1:c.4139G>A NP_001394616.1:p.Ser1380Asn missense NM_001407688.1:c.4142G>A NP_001394617.1:p.Ser1381Asn missense NM_001407689.1:c.4142G>A NP_001394618.1:p.Ser1381Asn missense NM_001407690.1:c.4139G>A NP_001394619.1:p.Ser1380Asn missense NM_001407691.1:c.4139G>A NP_001394620.1:p.Ser1380Asn missense NM_001407692.1:c.4127G>A NP_001394621.1:p.Ser1376Asn missense NM_001407694.1:c.4127G>A NP_001394623.1:p.Ser1376Asn missense NM_001407695.1:c.4127G>A NP_001394624.1:p.Ser1376Asn missense NM_001407696.1:c.4127G>A NP_001394625.1:p.Ser1376Asn missense NM_001407697.1:c.4127G>A NP_001394626.1:p.Ser1376Asn missense NM_001407698.1:c.4127G>A NP_001394627.1:p.Ser1376Asn missense NM_001407724.1:c.4127G>A NP_001394653.1:p.Ser1376Asn missense NM_001407725.1:c.4127G>A NP_001394654.1:p.Ser1376Asn missense NM_001407726.1:c.4127G>A NP_001394655.1:p.Ser1376Asn missense NM_001407727.1:c.4127G>A NP_001394656.1:p.Ser1376Asn missense NM_001407728.1:c.4127G>A NP_001394657.1:p.Ser1376Asn missense NM_001407729.1:c.4127G>A NP_001394658.1:p.Ser1376Asn missense NM_001407730.1:c.4127G>A NP_001394659.1:p.Ser1376Asn missense NM_001407731.1:c.4127G>A NP_001394660.1:p.Ser1376Asn missense NM_001407732.1:c.4127G>A NP_001394661.1:p.Ser1376Asn missense NM_001407733.1:c.4127G>A NP_001394662.1:p.Ser1376Asn missense NM_001407734.1:c.4127G>A NP_001394663.1:p.Ser1376Asn missense NM_001407735.1:c.4127G>A NP_001394664.1:p.Ser1376Asn missense NM_001407736.1:c.4127G>A NP_001394665.1:p.Ser1376Asn missense NM_001407737.1:c.4127G>A NP_001394666.1:p.Ser1376Asn missense NM_001407738.1:c.4127G>A NP_001394667.1:p.Ser1376Asn missense NM_001407739.1:c.4127G>A NP_001394668.1:p.Ser1376Asn missense NM_001407740.1:c.4124G>A NP_001394669.1:p.Ser1375Asn missense NM_001407741.1:c.4124G>A NP_001394670.1:p.Ser1375Asn missense NM_001407742.1:c.4124G>A NP_001394671.1:p.Ser1375Asn missense NM_001407743.1:c.4124G>A NP_001394672.1:p.Ser1375Asn missense NM_001407744.1:c.4124G>A NP_001394673.1:p.Ser1375Asn missense NM_001407745.1:c.4124G>A NP_001394674.1:p.Ser1375Asn missense NM_001407746.1:c.4124G>A NP_001394675.1:p.Ser1375Asn missense NM_001407747.1:c.4124G>A NP_001394676.1:p.Ser1375Asn missense NM_001407748.1:c.4124G>A NP_001394677.1:p.Ser1375Asn missense NM_001407749.1:c.4124G>A NP_001394678.1:p.Ser1375Asn missense NM_001407750.1:c.4124G>A NP_001394679.1:p.Ser1375Asn missense NM_001407751.1:c.4124G>A NP_001394680.1:p.Ser1375Asn missense NM_001407752.1:c.4124G>A NP_001394681.1:p.Ser1375Asn missense NM_001407838.1:c.4124G>A NP_001394767.1:p.Ser1375Asn missense NM_001407839.1:c.4124G>A NP_001394768.1:p.Ser1375Asn missense NM_001407841.1:c.4124G>A NP_001394770.1:p.Ser1375Asn missense NM_001407842.1:c.4124G>A NP_001394771.1:p.Ser1375Asn missense NM_001407843.1:c.4124G>A NP_001394772.1:p.Ser1375Asn missense NM_001407844.1:c.4124G>A NP_001394773.1:p.Ser1375Asn missense NM_001407845.1:c.4124G>A NP_001394774.1:p.Ser1375Asn missense NM_001407846.1:c.4124G>A NP_001394775.1:p.Ser1375Asn missense NM_001407847.1:c.4121G>A NP_001394776.1:p.Ser1374Asn missense NM_001407848.1:c.4121G>A NP_001394777.1:p.Ser1374Asn missense NM_001407849.1:c.4121G>A NP_001394778.1:p.Ser1374Asn missense NM_001407850.1:c.4124G>A NP_001394779.1:p.Ser1375Asn missense NM_001407851.1:c.4124G>A NP_001394780.1:p.Ser1375Asn missense NM_001407852.1:c.4124G>A NP_001394781.1:p.Ser1375Asn missense NM_001407853.1:c.4055G>A NP_001394782.1:p.Ser1352Asn missense NM_001407854.1:c.4268G>A NP_001394783.1:p.Ser1423Asn missense NM_001407858.1:c.4268G>A NP_001394787.1:p.Ser1423Asn missense NM_001407859.1:c.4268G>A NP_001394788.1:p.Ser1423Asn missense NM_001407860.1:c.4265G>A NP_001394789.1:p.Ser1422Asn missense NM_001407861.1:c.4265G>A NP_001394790.1:p.Ser1422Asn missense NM_001407862.1:c.4067G>A NP_001394791.1:p.Ser1356Asn missense NM_001407863.1:c.4145G>A NP_001394792.1:p.Ser1382Asn missense NM_001407874.1:c.4064G>A NP_001394803.1:p.Ser1355Asn missense NM_001407875.1:c.4064G>A NP_001394804.1:p.Ser1355Asn missense NM_001407879.1:c.4058G>A NP_001394808.1:p.Ser1353Asn missense NM_001407881.1:c.4058G>A NP_001394810.1:p.Ser1353Asn missense NM_001407882.1:c.4058G>A NP_001394811.1:p.Ser1353Asn missense NM_001407884.1:c.4058G>A NP_001394813.1:p.Ser1353Asn missense NM_001407885.1:c.4058G>A NP_001394814.1:p.Ser1353Asn missense NM_001407886.1:c.4058G>A NP_001394815.1:p.Ser1353Asn missense NM_001407887.1:c.4058G>A NP_001394816.1:p.Ser1353Asn missense NM_001407889.1:c.4058G>A NP_001394818.1:p.Ser1353Asn missense NM_001407894.1:c.4055G>A NP_001394823.1:p.Ser1352Asn missense NM_001407895.1:c.4055G>A NP_001394824.1:p.Ser1352Asn missense NM_001407896.1:c.4055G>A NP_001394825.1:p.Ser1352Asn missense NM_001407897.1:c.4055G>A NP_001394826.1:p.Ser1352Asn missense NM_001407898.1:c.4055G>A NP_001394827.1:p.Ser1352Asn missense NM_001407899.1:c.4055G>A NP_001394828.1:p.Ser1352Asn missense NM_001407900.1:c.4058G>A NP_001394829.1:p.Ser1353Asn missense NM_001407902.1:c.4058G>A NP_001394831.1:p.Ser1353Asn missense NM_001407904.1:c.4058G>A NP_001394833.1:p.Ser1353Asn missense NM_001407906.1:c.4058G>A NP_001394835.1:p.Ser1353Asn missense NM_001407907.1:c.4055G>A NP_001394836.1:p.Ser1352Asn missense NM_001407908.1:c.4055G>A NP_001394837.1:p.Ser1352Asn missense NM_001407909.1:c.4055G>A NP_001394838.1:p.Ser1352Asn missense NM_001407910.1:c.4055G>A NP_001394839.1:p.Ser1352Asn missense NM_001407915.1:c.4052G>A NP_001394844.1:p.Ser1351Asn missense NM_001407916.1:c.4055G>A NP_001394845.1:p.Ser1352Asn missense NM_001407917.1:c.4055G>A NP_001394846.1:p.Ser1352Asn missense NM_001407918.1:c.4055G>A NP_001394847.1:p.Ser1352Asn missense NM_001407919.1:c.4145G>A NP_001394848.1:p.Ser1382Asn missense NM_001407920.1:c.4004G>A NP_001394849.1:p.Ser1335Asn missense NM_001407921.1:c.4004G>A NP_001394850.1:p.Ser1335Asn missense NM_001407922.1:c.4004G>A NP_001394851.1:p.Ser1335Asn missense NM_001407923.1:c.4004G>A NP_001394852.1:p.Ser1335Asn missense NM_001407924.1:c.4004G>A NP_001394853.1:p.Ser1335Asn missense NM_001407925.1:c.4004G>A NP_001394854.1:p.Ser1335Asn missense NM_001407926.1:c.4004G>A NP_001394855.1:p.Ser1335Asn missense NM_001407927.1:c.4004G>A NP_001394856.1:p.Ser1335Asn missense NM_001407928.1:c.4004G>A NP_001394857.1:p.Ser1335Asn missense NM_001407929.1:c.4004G>A NP_001394858.1:p.Ser1335Asn missense NM_001407930.1:c.4001G>A NP_001394859.1:p.Ser1334Asn missense NM_001407931.1:c.4001G>A NP_001394860.1:p.Ser1334Asn missense NM_001407932.1:c.4001G>A NP_001394861.1:p.Ser1334Asn missense NM_001407933.1:c.4001G>A NP_001394862.1:p.Ser1334Asn missense NM_001407934.1:c.3998G>A NP_001394863.1:p.Ser1333Asn missense NM_001407935.1:c.4001G>A NP_001394864.1:p.Ser1334Asn missense NM_001407936.1:c.4001G>A NP_001394865.1:p.Ser1334Asn missense NM_001407937.1:c.4145G>A NP_001394866.1:p.Ser1382Asn missense NM_001407938.1:c.4145G>A NP_001394867.1:p.Ser1382Asn missense NM_001407939.1:c.4145G>A NP_001394868.1:p.Ser1382Asn missense NM_001407940.1:c.4142G>A NP_001394869.1:p.Ser1381Asn missense NM_001407941.1:c.4142G>A NP_001394870.1:p.Ser1381Asn missense NM_001407942.1:c.4127G>A NP_001394871.1:p.Ser1376Asn missense NM_001407943.1:c.4124G>A NP_001394872.1:p.Ser1375Asn missense NM_001407944.1:c.4127G>A NP_001394873.1:p.Ser1376Asn missense NM_001407945.1:c.4127G>A NP_001394874.1:p.Ser1376Asn missense NM_001407946.1:c.3935G>A NP_001394875.1:p.Ser1312Asn missense NM_001407947.1:c.3935G>A NP_001394876.1:p.Ser1312Asn missense NM_001407948.1:c.3935G>A NP_001394877.1:p.Ser1312Asn missense NM_001407949.1:c.3935G>A NP_001394878.1:p.Ser1312Asn missense NM_001407950.1:c.3935G>A NP_001394879.1:p.Ser1312Asn missense NM_001407951.1:c.3935G>A NP_001394880.1:p.Ser1312Asn missense NM_001407952.1:c.3932G>A NP_001394881.1:p.Ser1311Asn missense NM_001407953.1:c.3932G>A NP_001394882.1:p.Ser1311Asn missense NM_001407954.1:c.3932G>A NP_001394883.1:p.Ser1311Asn missense NM_001407955.1:c.3932G>A NP_001394884.1:p.Ser1311Asn missense NM_001407956.1:c.3929G>A NP_001394885.1:p.Ser1310Asn missense NM_001407957.1:c.3932G>A NP_001394886.1:p.Ser1311Asn missense NM_001407958.1:c.3932G>A NP_001394887.1:p.Ser1311Asn missense NM_001407959.1:c.3887G>A NP_001394888.1:p.Ser1296Asn missense NM_001407960.1:c.3887G>A NP_001394889.1:p.Ser1296Asn missense NM_001407962.1:c.3884G>A NP_001394891.1:p.Ser1295Asn missense NM_001407963.1:c.3884G>A NP_001394892.1:p.Ser1295Asn missense NM_001407964.1:c.4124G>A NP_001394893.1:p.Ser1375Asn missense NM_001407965.1:c.3761G>A NP_001394894.1:p.Ser1254Asn missense NM_001407966.1:c.3380G>A NP_001394895.1:p.Ser1127Asn missense NM_001407967.1:c.3380G>A NP_001394896.1:p.Ser1127Asn missense NM_001407968.1:c.1664G>A NP_001394897.1:p.Ser555Asn missense NM_001407969.1:c.1661G>A NP_001394898.1:p.Ser554Asn missense NM_001407970.1:c.959G>A NP_001394899.1:p.Ser320Asn missense NM_001407971.1:c.959G>A NP_001394900.1:p.Ser320Asn missense NM_001407972.1:c.956G>A NP_001394901.1:p.Ser319Asn missense NM_001407973.1:c.959G>A NP_001394902.1:p.Ser320Asn missense NM_001407974.1:c.959G>A NP_001394903.1:p.Ser320Asn missense NM_001407975.1:c.959G>A NP_001394904.1:p.Ser320Asn missense NM_001407976.1:c.959G>A NP_001394905.1:p.Ser320Asn missense NM_001407977.1:c.959G>A NP_001394906.1:p.Ser320Asn missense NM_001407978.1:c.959G>A NP_001394907.1:p.Ser320Asn missense NM_001407979.1:c.956G>A NP_001394908.1:p.Ser319Asn missense NM_001407980.1:c.956G>A NP_001394909.1:p.Ser319Asn missense NM_001407981.1:c.956G>A NP_001394910.1:p.Ser319Asn missense NM_001407982.1:c.956G>A NP_001394911.1:p.Ser319Asn missense NM_001407983.1:c.956G>A NP_001394912.1:p.Ser319Asn missense NM_001407984.1:c.956G>A NP_001394913.1:p.Ser319Asn missense NM_001407985.1:c.956G>A NP_001394914.1:p.Ser319Asn missense NM_001407986.1:c.956G>A NP_001394915.1:p.Ser319Asn missense NM_001407990.1:c.956G>A NP_001394919.1:p.Ser319Asn missense NM_001407991.1:c.956G>A NP_001394920.1:p.Ser319Asn missense NM_001407992.1:c.956G>A NP_001394921.1:p.Ser319Asn missense NM_001407993.1:c.959G>A NP_001394922.1:p.Ser320Asn missense NM_001408392.1:c.956G>A NP_001395321.1:p.Ser319Asn missense NM_001408396.1:c.956G>A NP_001395325.1:p.Ser319Asn missense NM_001408397.1:c.956G>A NP_001395326.1:p.Ser319Asn missense NM_001408398.1:c.956G>A NP_001395327.1:p.Ser319Asn missense NM_001408399.1:c.956G>A NP_001395328.1:p.Ser319Asn missense NM_001408400.1:c.953G>A NP_001395329.1:p.Ser318Asn missense NM_001408401.1:c.953G>A NP_001395330.1:p.Ser318Asn missense NM_001408402.1:c.953G>A NP_001395331.1:p.Ser318Asn missense NM_001408403.1:c.956G>A NP_001395332.1:p.Ser319Asn missense NM_001408404.1:c.956G>A NP_001395333.1:p.Ser319Asn missense NM_001408406.1:c.950G>A NP_001395335.1:p.Ser317Asn missense NM_001408407.1:c.953G>A NP_001395336.1:p.Ser318Asn missense NM_001408408.1:c.950G>A NP_001395337.1:p.Ser317Asn missense NM_001408409.1:c.881G>A NP_001395338.1:p.Ser294Asn missense NM_001408410.1:c.818G>A NP_001395339.1:p.Ser273Asn missense NM_001408411.1:c.881G>A NP_001395340.1:p.Ser294Asn missense NM_001408412.1:c.881G>A NP_001395341.1:p.Ser294Asn missense NM_001408413.1:c.878G>A NP_001395342.1:p.Ser293Asn missense NM_001408414.1:c.881G>A NP_001395343.1:p.Ser294Asn missense NM_001408415.1:c.881G>A NP_001395344.1:p.Ser294Asn missense NM_001408416.1:c.878G>A NP_001395345.1:p.Ser293Asn missense NM_001408418.1:c.842G>A NP_001395347.1:p.Ser281Asn missense NM_001408419.1:c.842G>A NP_001395348.1:p.Ser281Asn missense NM_001408420.1:c.842G>A NP_001395349.1:p.Ser281Asn missense NM_001408421.1:c.839G>A NP_001395350.1:p.Ser280Asn missense NM_001408422.1:c.842G>A NP_001395351.1:p.Ser281Asn missense NM_001408423.1:c.842G>A NP_001395352.1:p.Ser281Asn missense NM_001408424.1:c.839G>A NP_001395353.1:p.Ser280Asn missense NM_001408425.1:c.836G>A NP_001395354.1:p.Ser279Asn missense NM_001408426.1:c.836G>A NP_001395355.1:p.Ser279Asn missense NM_001408427.1:c.836G>A NP_001395356.1:p.Ser279Asn missense NM_001408428.1:c.836G>A NP_001395357.1:p.Ser279Asn missense NM_001408429.1:c.836G>A NP_001395358.1:p.Ser279Asn missense NM_001408430.1:c.836G>A NP_001395359.1:p.Ser279Asn missense NM_001408431.1:c.839G>A NP_001395360.1:p.Ser280Asn missense NM_001408432.1:c.833G>A NP_001395361.1:p.Ser278Asn missense NM_001408433.1:c.833G>A NP_001395362.1:p.Ser278Asn missense NM_001408434.1:c.833G>A NP_001395363.1:p.Ser278Asn missense NM_001408435.1:c.833G>A NP_001395364.1:p.Ser278Asn missense NM_001408436.1:c.836G>A NP_001395365.1:p.Ser279Asn missense NM_001408437.1:c.836G>A NP_001395366.1:p.Ser279Asn missense NM_001408438.1:c.836G>A NP_001395367.1:p.Ser279Asn missense NM_001408439.1:c.836G>A NP_001395368.1:p.Ser279Asn missense NM_001408440.1:c.836G>A NP_001395369.1:p.Ser279Asn missense NM_001408441.1:c.833G>A NP_001395370.1:p.Ser278Asn missense NM_001408442.1:c.833G>A NP_001395371.1:p.Ser278Asn missense NM_001408443.1:c.833G>A NP_001395372.1:p.Ser278Asn missense NM_001408444.1:c.833G>A NP_001395373.1:p.Ser278Asn missense NM_001408445.1:c.833G>A NP_001395374.1:p.Ser278Asn missense NM_001408446.1:c.833G>A NP_001395375.1:p.Ser278Asn missense NM_001408447.1:c.833G>A NP_001395376.1:p.Ser278Asn missense NM_001408448.1:c.833G>A NP_001395377.1:p.Ser278Asn missense NM_001408450.1:c.833G>A NP_001395379.1:p.Ser278Asn missense NM_001408451.1:c.824G>A NP_001395380.1:p.Ser275Asn missense NM_001408452.1:c.818G>A NP_001395381.1:p.Ser273Asn missense NM_001408453.1:c.818G>A NP_001395382.1:p.Ser273Asn missense NM_001408454.1:c.818G>A NP_001395383.1:p.Ser273Asn missense NM_001408455.1:c.818G>A NP_001395384.1:p.Ser273Asn missense NM_001408456.1:c.818G>A NP_001395385.1:p.Ser273Asn missense NM_001408457.1:c.818G>A NP_001395386.1:p.Ser273Asn missense NM_001408458.1:c.818G>A NP_001395387.1:p.Ser273Asn missense NM_001408459.1:c.818G>A NP_001395388.1:p.Ser273Asn missense NM_001408460.1:c.818G>A NP_001395389.1:p.Ser273Asn missense NM_001408461.1:c.818G>A NP_001395390.1:p.Ser273Asn missense NM_001408462.1:c.815G>A NP_001395391.1:p.Ser272Asn missense NM_001408463.1:c.815G>A NP_001395392.1:p.Ser272Asn missense NM_001408464.1:c.815G>A NP_001395393.1:p.Ser272Asn missense NM_001408465.1:c.815G>A NP_001395394.1:p.Ser272Asn missense NM_001408466.1:c.815G>A NP_001395395.1:p.Ser272Asn missense NM_001408467.1:c.815G>A NP_001395396.1:p.Ser272Asn missense NM_001408468.1:c.815G>A NP_001395397.1:p.Ser272Asn missense NM_001408469.1:c.815G>A NP_001395398.1:p.Ser272Asn missense NM_001408470.1:c.812G>A NP_001395399.1:p.Ser271Asn missense NM_001408472.1:c.956G>A NP_001395401.1:p.Ser319Asn missense NM_001408473.1:c.956G>A NP_001395402.1:p.Ser319Asn missense NM_001408474.1:c.758G>A NP_001395403.1:p.Ser253Asn missense NM_001408475.1:c.755G>A NP_001395404.1:p.Ser252Asn missense NM_001408476.1:c.758G>A NP_001395405.1:p.Ser253Asn missense NM_001408478.1:c.749G>A NP_001395407.1:p.Ser250Asn missense NM_001408479.1:c.749G>A NP_001395408.1:p.Ser250Asn missense NM_001408480.1:c.749G>A NP_001395409.1:p.Ser250Asn missense NM_001408481.1:c.749G>A NP_001395410.1:p.Ser250Asn missense NM_001408482.1:c.749G>A NP_001395411.1:p.Ser250Asn missense NM_001408483.1:c.749G>A NP_001395412.1:p.Ser250Asn missense NM_001408484.1:c.749G>A NP_001395413.1:p.Ser250Asn missense NM_001408485.1:c.749G>A NP_001395414.1:p.Ser250Asn missense NM_001408489.1:c.746G>A NP_001395418.1:p.Ser249Asn missense NM_001408490.1:c.746G>A NP_001395419.1:p.Ser249Asn missense NM_001408491.1:c.746G>A NP_001395420.1:p.Ser249Asn missense NM_001408492.1:c.746G>A NP_001395421.1:p.Ser249Asn missense NM_001408493.1:c.746G>A NP_001395422.1:p.Ser249Asn missense NM_001408494.1:c.719G>A NP_001395423.1:p.Ser240Asn missense NM_001408495.1:c.716G>A NP_001395424.1:p.Ser239Asn missense NM_001408496.1:c.695G>A NP_001395425.1:p.Ser232Asn missense NM_001408497.1:c.695G>A NP_001395426.1:p.Ser232Asn missense NM_001408498.1:c.695G>A NP_001395427.1:p.Ser232Asn missense NM_001408499.1:c.695G>A NP_001395428.1:p.Ser232Asn missense NM_001408500.1:c.695G>A NP_001395429.1:p.Ser232Asn missense NM_001408501.1:c.695G>A NP_001395430.1:p.Ser232Asn missense NM_001408502.1:c.626G>A NP_001395431.1:p.Ser209Asn missense NM_001408503.1:c.692G>A NP_001395432.1:p.Ser231Asn missense NM_001408504.1:c.692G>A NP_001395433.1:p.Ser231Asn missense NM_001408505.1:c.692G>A NP_001395434.1:p.Ser231Asn missense NM_001408506.1:c.632G>A NP_001395435.1:p.Ser211Asn missense NM_001408507.1:c.629G>A NP_001395436.1:p.Ser210Asn missense NM_001408508.1:c.620G>A NP_001395437.1:p.Ser207Asn missense NM_001408509.1:c.620G>A NP_001395438.1:p.Ser207Asn missense NM_001408510.1:c.578G>A NP_001395439.1:p.Ser193Asn missense NM_001408511.1:c.575G>A NP_001395440.1:p.Ser192Asn missense NM_001408512.1:c.455G>A NP_001395441.1:p.Ser152Asn missense NM_001408513.1:c.746G>A NP_001395442.1:p.Ser249Asn missense NM_001408514.1:c.749G>A NP_001395443.1:p.Ser250Asn missense NM_007297.4:c.4127G>A NP_009228.2:p.Ser1376Asn missense NM_007298.4:c.959G>A NP_009229.2:p.Ser320Asn missense NM_007299.4:c.959G>A NP_009230.2:p.Ser320Asn missense NM_007300.4:c.4268G>A NP_009231.2:p.Ser1423Asn missense NM_007304.2:c.959G>A NP_009235.2:p.Ser320Asn missense NR_027676.2:n.4445G>A non-coding transcript variant NC_000017.11:g.43082493C>T NC_000017.10:g.41234510C>T NG_005905.2:g.135491G>A LRG_292:g.135491G>A LRG_292t1:c.4268G>A LRG_292p1:p.Ser1423Asn - Protein change
- S1423N, S1376N, S320N, S1254N, S1334N, S1335N, S1351N, S1352N, S1382N, S1395N, S1422N, S211N, S240N, S250N, S253N, S281N, S319N, S152N, S192N, S231N, S252N, S271N, S278N, S279N, S280N, S293N, S318N, S1310N, S1333N, S1353N, S1355N, S1374N, S1375N, S1381N, S1421N, S207N, S232N, S273N, S275N, S294N, S555N, S1127N, S1296N, S1311N, S1312N, S1356N, S1419N, S1295N, S1380N, S1396N, S1397N, S193N, S209N, S210N, S239N, S249N, S272N, S317N, S554N
- Other names
- -
- Canonical SPDI
- NC_000017.11:43082492:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13050 | 14856 | |
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
|
Jan 9, 2024 | RCV001217906.7 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 17, 2024 | RCV002327509.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Feb 9, 2021 | RCV003145403.3 | |
|
BRCA1-related disorder
|
Uncertain significance (1) |
no assertion criteria provided
|
Aug 4, 2024 | RCV004731104.1 |
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 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003830130.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Uncertain significance
(Jan 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001389765.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1423 of the BRCA1 protein (p.Ser1423Asn). … (more)
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1423 of the BRCA1 protein (p.Ser1423Asn). 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: 946942). 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%. 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
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002627792.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.S1423N variant (also known as c.4268G>A), located in coding exon 11 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The p.S1423N variant (also known as c.4268G>A), located in coding exon 11 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4268. The serine at codon 1423 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Aug 04, 2024)
|
no assertion criteria provided
Method: clinical testing
|
BRCA1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV005336602.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The BRCA1 c.4268G>A variant is predicted to result in the amino acid substitution p.Ser1423Asn. This variant was reported in an individual with breast cancer (Okawa … (more)
The BRCA1 c.4268G>A variant is predicted to result in the amino acid substitution p.Ser1423Asn. This variant was reported in an individual with breast cancer (Okawa et al 2022. PubMed ID: 36243179, Supplementary Table 2). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
|
Comment:
Comment:
The p.S1423N variant (also known as c.4268G>A), located in coding exon 11 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4268. The serine at codon 1423 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
The BRCA1 c.4268G>A variant is predicted to result in the amino acid substitution p.Ser1423Asn. This variant was reported in an individual with breast cancer (Okawa et al 2022. PubMed ID: 36243179, Supplementary Table 2). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1423 of the BRCA1 protein (p.Ser1423Asn). 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: 946942). 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%. 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.S1423N variant (also known as c.4268G>A), located in coding exon 11 of the BRCA1 gene, results from a G to A substitution at nucleotide position 4268. The serine at codon 1423 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
The BRCA1 c.4268G>A variant is predicted to result in the amino acid substitution p.Ser1423Asn. This variant was reported in an individual with breast cancer (Okawa et al 2022. PubMed ID: 36243179, Supplementary Table 2). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs876660129 ...
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Record last updated Oct 08, 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.