The p.T1700I variant (also known as c.5099C>T), located in coding exon 16 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5099. The threonine at codon 1700 is replaced by isoleucine, an amino acid with similar properties. One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Another functional assay determined this alteration to be deficient in homologous recombination repair activity (Petitalot A et al. Mol Cancer Res, 2019 01;17:54-69). Based on internal structural analysis, this variant is anticipated to disrupt a region of known function (Ambry internal data; Wu Q et al. Mol Cell 2016 Feb;61(3):434-448; Tram E et al. PLoS One 2013 May;8(5):e62468). Another alteration at the same codon, p.T1700A (c.5098A>G), has also been determined to be functionally and structurally deleterious (Ambry internal data; Findlay GM et al. Nature, 2018 10;562:217-222; Wu Q et al. Mol Cell 2016 Feb;61(3):434-448; Tram E et al. PLoS One 2013 May;8(5):e62468). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5099C>T (p.Thr1700Ile)
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.
(2)
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Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Likely pathogenic
2
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5099C>T (p.Thr1700Ile)
Variation ID: 864948 Accession: VCV000864948.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43063927 (GRCh38) [ NCBI UCSC ] 17: 41215944 (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 Apr 18, 2020 May 1, 2024 Nov 5, 2020 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5099C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Thr1700Ile missense NM_001407571.1:c.4886C>T NP_001394500.1:p.Thr1629Ile missense NM_001407581.1:c.5165C>T NP_001394510.1:p.Thr1722Ile missense NM_001407582.1:c.5165C>T NP_001394511.1:p.Thr1722Ile missense NM_001407583.1:c.5162C>T NP_001394512.1:p.Thr1721Ile missense NM_001407585.1:c.5162C>T NP_001394514.1:p.Thr1721Ile missense NM_001407587.1:c.5162C>T NP_001394516.1:p.Thr1721Ile missense NM_001407590.1:c.5159C>T NP_001394519.1:p.Thr1720Ile missense NM_001407591.1:c.5159C>T NP_001394520.1:p.Thr1720Ile missense NM_001407593.1:c.5099C>T NP_001394522.1:p.Thr1700Ile missense NM_001407594.1:c.5099C>T NP_001394523.1:p.Thr1700Ile missense NM_001407596.1:c.5099C>T NP_001394525.1:p.Thr1700Ile missense NM_001407597.1:c.5099C>T NP_001394526.1:p.Thr1700Ile missense NM_001407598.1:c.5099C>T NP_001394527.1:p.Thr1700Ile missense NM_001407602.1:c.5099C>T NP_001394531.1:p.Thr1700Ile missense NM_001407603.1:c.5099C>T NP_001394532.1:p.Thr1700Ile missense NM_001407605.1:c.5099C>T NP_001394534.1:p.Thr1700Ile missense NM_001407610.1:c.5096C>T NP_001394539.1:p.Thr1699Ile missense NM_001407611.1:c.5096C>T NP_001394540.1:p.Thr1699Ile missense NM_001407612.1:c.5096C>T NP_001394541.1:p.Thr1699Ile missense NM_001407613.1:c.5096C>T NP_001394542.1:p.Thr1699Ile missense NM_001407614.1:c.5096C>T NP_001394543.1:p.Thr1699Ile missense NM_001407615.1:c.5096C>T NP_001394544.1:p.Thr1699Ile missense NM_001407616.1:c.5096C>T NP_001394545.1:p.Thr1699Ile missense NM_001407617.1:c.5096C>T NP_001394546.1:p.Thr1699Ile missense NM_001407618.1:c.5096C>T NP_001394547.1:p.Thr1699Ile missense NM_001407619.1:c.5096C>T NP_001394548.1:p.Thr1699Ile missense NM_001407620.1:c.5096C>T NP_001394549.1:p.Thr1699Ile missense NM_001407621.1:c.5096C>T NP_001394550.1:p.Thr1699Ile missense NM_001407622.1:c.5096C>T NP_001394551.1:p.Thr1699Ile missense NM_001407623.1:c.5096C>T NP_001394552.1:p.Thr1699Ile missense NM_001407624.1:c.5096C>T NP_001394553.1:p.Thr1699Ile missense NM_001407625.1:c.5096C>T NP_001394554.1:p.Thr1699Ile missense NM_001407626.1:c.5096C>T NP_001394555.1:p.Thr1699Ile missense NM_001407627.1:c.5093C>T NP_001394556.1:p.Thr1698Ile missense NM_001407628.1:c.5093C>T NP_001394557.1:p.Thr1698Ile missense NM_001407629.1:c.5093C>T NP_001394558.1:p.Thr1698Ile missense NM_001407630.1:c.5093C>T NP_001394559.1:p.Thr1698Ile missense NM_001407631.1:c.5093C>T NP_001394560.1:p.Thr1698Ile missense NM_001407632.1:c.5093C>T NP_001394561.1:p.Thr1698Ile missense NM_001407633.1:c.5093C>T NP_001394562.1:p.Thr1698Ile missense NM_001407634.1:c.5093C>T NP_001394563.1:p.Thr1698Ile missense NM_001407635.1:c.5093C>T NP_001394564.1:p.Thr1698Ile missense NM_001407636.1:c.5093C>T NP_001394565.1:p.Thr1698Ile missense NM_001407637.1:c.5093C>T NP_001394566.1:p.Thr1698Ile missense NM_001407638.1:c.5093C>T NP_001394567.1:p.Thr1698Ile missense NM_001407639.1:c.5093C>T NP_001394568.1:p.Thr1698Ile missense NM_001407640.1:c.5093C>T NP_001394569.1:p.Thr1698Ile missense NM_001407641.1:c.5093C>T NP_001394570.1:p.Thr1698Ile missense NM_001407642.1:c.5093C>T NP_001394571.1:p.Thr1698Ile missense NM_001407644.1:c.5090C>T NP_001394573.1:p.Thr1697Ile missense NM_001407645.1:c.5090C>T NP_001394574.1:p.Thr1697Ile missense NM_001407646.1:c.5087C>T NP_001394575.1:p.Thr1696Ile missense NM_001407647.1:c.5084C>T NP_001394576.1:p.Thr1695Ile missense NM_001407648.1:c.5042C>T NP_001394577.1:p.Thr1681Ile missense NM_001407649.1:c.5039C>T NP_001394578.1:p.Thr1680Ile missense NM_001407653.1:c.5021C>T NP_001394582.1:p.Thr1674Ile missense NM_001407654.1:c.5021C>T NP_001394583.1:p.Thr1674Ile missense NM_001407655.1:c.5021C>T NP_001394584.1:p.Thr1674Ile missense NM_001407656.1:c.5018C>T NP_001394585.1:p.Thr1673Ile missense NM_001407657.1:c.5018C>T NP_001394586.1:p.Thr1673Ile missense NM_001407658.1:c.5018C>T NP_001394587.1:p.Thr1673Ile missense NM_001407659.1:c.5015C>T NP_001394588.1:p.Thr1672Ile missense NM_001407660.1:c.5015C>T NP_001394589.1:p.Thr1672Ile missense NM_001407661.1:c.5015C>T NP_001394590.1:p.Thr1672Ile missense NM_001407662.1:c.5015C>T NP_001394591.1:p.Thr1672Ile missense NM_001407663.1:c.5015C>T NP_001394592.1:p.Thr1672Ile missense NM_001407664.1:c.4976C>T NP_001394593.1:p.Thr1659Ile missense NM_001407665.1:c.4976C>T NP_001394594.1:p.Thr1659Ile missense NM_001407666.1:c.4976C>T NP_001394595.1:p.Thr1659Ile missense NM_001407667.1:c.4976C>T NP_001394596.1:p.Thr1659Ile missense NM_001407668.1:c.4976C>T NP_001394597.1:p.Thr1659Ile missense NM_001407669.1:c.4976C>T NP_001394598.1:p.Thr1659Ile missense NM_001407670.1:c.4973C>T NP_001394599.1:p.Thr1658Ile missense NM_001407671.1:c.4973C>T NP_001394600.1:p.Thr1658Ile missense NM_001407672.1:c.4973C>T NP_001394601.1:p.Thr1658Ile missense NM_001407673.1:c.4973C>T NP_001394602.1:p.Thr1658Ile missense NM_001407674.1:c.4973C>T NP_001394603.1:p.Thr1658Ile missense NM_001407675.1:c.4973C>T NP_001394604.1:p.Thr1658Ile missense NM_001407676.1:c.4973C>T NP_001394605.1:p.Thr1658Ile missense NM_001407677.1:c.4973C>T NP_001394606.1:p.Thr1658Ile missense NM_001407678.1:c.4973C>T NP_001394607.1:p.Thr1658Ile missense NM_001407679.1:c.4973C>T NP_001394608.1:p.Thr1658Ile missense NM_001407680.1:c.4973C>T NP_001394609.1:p.Thr1658Ile missense NM_001407681.1:c.4970C>T NP_001394610.1:p.Thr1657Ile missense NM_001407682.1:c.4970C>T NP_001394611.1:p.Thr1657Ile missense NM_001407683.1:c.4970C>T NP_001394612.1:p.Thr1657Ile missense NM_001407684.1:c.5099C>T NP_001394613.1:p.Thr1700Ile missense NM_001407685.1:c.4970C>T NP_001394614.1:p.Thr1657Ile missense NM_001407686.1:c.4970C>T NP_001394615.1:p.Thr1657Ile missense NM_001407687.1:c.4970C>T NP_001394616.1:p.Thr1657Ile missense NM_001407688.1:c.4970C>T NP_001394617.1:p.Thr1657Ile missense NM_001407689.1:c.4970C>T NP_001394618.1:p.Thr1657Ile missense NM_001407690.1:c.4967C>T NP_001394619.1:p.Thr1656Ile missense NM_001407691.1:c.4967C>T NP_001394620.1:p.Thr1656Ile missense NM_001407692.1:c.4958C>T NP_001394621.1:p.Thr1653Ile missense NM_001407694.1:c.4958C>T NP_001394623.1:p.Thr1653Ile missense NM_001407695.1:c.4958C>T NP_001394624.1:p.Thr1653Ile missense NM_001407696.1:c.4958C>T NP_001394625.1:p.Thr1653Ile missense NM_001407697.1:c.4958C>T NP_001394626.1:p.Thr1653Ile missense NM_001407698.1:c.4958C>T NP_001394627.1:p.Thr1653Ile missense NM_001407724.1:c.4958C>T NP_001394653.1:p.Thr1653Ile missense NM_001407725.1:c.4958C>T NP_001394654.1:p.Thr1653Ile missense NM_001407726.1:c.4958C>T NP_001394655.1:p.Thr1653Ile missense NM_001407727.1:c.4958C>T NP_001394656.1:p.Thr1653Ile missense NM_001407728.1:c.4958C>T NP_001394657.1:p.Thr1653Ile missense NM_001407729.1:c.4958C>T NP_001394658.1:p.Thr1653Ile missense NM_001407730.1:c.4958C>T NP_001394659.1:p.Thr1653Ile missense NM_001407731.1:c.4958C>T NP_001394660.1:p.Thr1653Ile missense NM_001407732.1:c.4955C>T NP_001394661.1:p.Thr1652Ile missense NM_001407733.1:c.4955C>T NP_001394662.1:p.Thr1652Ile missense NM_001407734.1:c.4955C>T NP_001394663.1:p.Thr1652Ile missense NM_001407735.1:c.4955C>T NP_001394664.1:p.Thr1652Ile missense NM_001407736.1:c.4955C>T NP_001394665.1:p.Thr1652Ile missense NM_001407737.1:c.4955C>T NP_001394666.1:p.Thr1652Ile missense NM_001407738.1:c.4955C>T NP_001394667.1:p.Thr1652Ile missense NM_001407739.1:c.4955C>T NP_001394668.1:p.Thr1652Ile missense NM_001407740.1:c.4955C>T NP_001394669.1:p.Thr1652Ile missense NM_001407741.1:c.4955C>T NP_001394670.1:p.Thr1652Ile missense NM_001407742.1:c.4955C>T NP_001394671.1:p.Thr1652Ile missense NM_001407743.1:c.4955C>T NP_001394672.1:p.Thr1652Ile missense NM_001407744.1:c.4955C>T NP_001394673.1:p.Thr1652Ile missense NM_001407745.1:c.4955C>T NP_001394674.1:p.Thr1652Ile missense NM_001407746.1:c.4955C>T NP_001394675.1:p.Thr1652Ile missense NM_001407747.1:c.4955C>T NP_001394676.1:p.Thr1652Ile missense NM_001407748.1:c.4955C>T NP_001394677.1:p.Thr1652Ile missense NM_001407749.1:c.4955C>T NP_001394678.1:p.Thr1652Ile missense NM_001407750.1:c.4955C>T NP_001394679.1:p.Thr1652Ile missense NM_001407751.1:c.4955C>T NP_001394680.1:p.Thr1652Ile missense NM_001407752.1:c.4955C>T NP_001394681.1:p.Thr1652Ile missense NM_001407838.1:c.4952C>T NP_001394767.1:p.Thr1651Ile missense NM_001407839.1:c.4952C>T NP_001394768.1:p.Thr1651Ile missense NM_001407841.1:c.4952C>T NP_001394770.1:p.Thr1651Ile missense NM_001407842.1:c.4952C>T NP_001394771.1:p.Thr1651Ile missense NM_001407843.1:c.4952C>T NP_001394772.1:p.Thr1651Ile missense NM_001407844.1:c.4952C>T NP_001394773.1:p.Thr1651Ile missense NM_001407845.1:c.4952C>T NP_001394774.1:p.Thr1651Ile missense NM_001407846.1:c.4952C>T NP_001394775.1:p.Thr1651Ile missense NM_001407847.1:c.4952C>T NP_001394776.1:p.Thr1651Ile missense NM_001407848.1:c.4952C>T NP_001394777.1:p.Thr1651Ile missense NM_001407849.1:c.4952C>T NP_001394778.1:p.Thr1651Ile missense NM_001407850.1:c.4952C>T NP_001394779.1:p.Thr1651Ile missense NM_001407851.1:c.4952C>T NP_001394780.1:p.Thr1651Ile missense NM_001407852.1:c.4952C>T NP_001394781.1:p.Thr1651Ile missense NM_001407853.1:c.4952C>T NP_001394782.1:p.Thr1651Ile missense NM_001407854.1:c.5099C>T NP_001394783.1:p.Thr1700Ile missense NM_001407858.1:c.5096C>T NP_001394787.1:p.Thr1699Ile missense NM_001407859.1:c.5096C>T NP_001394788.1:p.Thr1699Ile missense NM_001407860.1:c.5096C>T NP_001394789.1:p.Thr1699Ile missense NM_001407861.1:c.5093C>T NP_001394790.1:p.Thr1698Ile missense NM_001407862.1:c.4898C>T NP_001394791.1:p.Thr1633Ile missense NM_001407874.1:c.4892C>T NP_001394803.1:p.Thr1631Ile missense NM_001407875.1:c.4892C>T NP_001394804.1:p.Thr1631Ile missense NM_001407879.1:c.4889C>T NP_001394808.1:p.Thr1630Ile missense NM_001407881.1:c.4889C>T NP_001394810.1:p.Thr1630Ile missense NM_001407882.1:c.4889C>T NP_001394811.1:p.Thr1630Ile missense NM_001407884.1:c.4889C>T NP_001394813.1:p.Thr1630Ile missense NM_001407885.1:c.4889C>T NP_001394814.1:p.Thr1630Ile missense NM_001407886.1:c.4889C>T NP_001394815.1:p.Thr1630Ile missense NM_001407887.1:c.4889C>T NP_001394816.1:p.Thr1630Ile missense NM_001407889.1:c.4889C>T NP_001394818.1:p.Thr1630Ile missense NM_001407894.1:c.4886C>T NP_001394823.1:p.Thr1629Ile missense NM_001407895.1:c.4886C>T NP_001394824.1:p.Thr1629Ile missense NM_001407896.1:c.4886C>T NP_001394825.1:p.Thr1629Ile missense NM_001407897.1:c.4886C>T NP_001394826.1:p.Thr1629Ile missense NM_001407898.1:c.4886C>T NP_001394827.1:p.Thr1629Ile missense NM_001407899.1:c.4886C>T NP_001394828.1:p.Thr1629Ile missense NM_001407900.1:c.4886C>T NP_001394829.1:p.Thr1629Ile missense NM_001407902.1:c.4886C>T NP_001394831.1:p.Thr1629Ile missense NM_001407904.1:c.4886C>T NP_001394833.1:p.Thr1629Ile missense NM_001407906.1:c.4886C>T NP_001394835.1:p.Thr1629Ile missense NM_001407907.1:c.4886C>T NP_001394836.1:p.Thr1629Ile missense NM_001407908.1:c.4886C>T NP_001394837.1:p.Thr1629Ile missense NM_001407909.1:c.4886C>T NP_001394838.1:p.Thr1629Ile missense NM_001407910.1:c.4886C>T NP_001394839.1:p.Thr1629Ile missense NM_001407915.1:c.4883C>T NP_001394844.1:p.Thr1628Ile missense NM_001407916.1:c.4883C>T NP_001394845.1:p.Thr1628Ile missense NM_001407917.1:c.4883C>T NP_001394846.1:p.Thr1628Ile missense NM_001407918.1:c.4883C>T NP_001394847.1:p.Thr1628Ile missense NM_001407919.1:c.4976C>T NP_001394848.1:p.Thr1659Ile missense NM_001407920.1:c.4835C>T NP_001394849.1:p.Thr1612Ile missense NM_001407921.1:c.4835C>T NP_001394850.1:p.Thr1612Ile missense NM_001407922.1:c.4835C>T NP_001394851.1:p.Thr1612Ile missense NM_001407923.1:c.4835C>T NP_001394852.1:p.Thr1612Ile missense NM_001407924.1:c.4835C>T NP_001394853.1:p.Thr1612Ile missense NM_001407925.1:c.4835C>T NP_001394854.1:p.Thr1612Ile missense NM_001407926.1:c.4835C>T NP_001394855.1:p.Thr1612Ile missense NM_001407927.1:c.4832C>T NP_001394856.1:p.Thr1611Ile missense NM_001407928.1:c.4832C>T NP_001394857.1:p.Thr1611Ile missense NM_001407929.1:c.4832C>T NP_001394858.1:p.Thr1611Ile missense NM_001407930.1:c.4832C>T NP_001394859.1:p.Thr1611Ile missense NM_001407931.1:c.4832C>T NP_001394860.1:p.Thr1611Ile missense NM_001407932.1:c.4832C>T NP_001394861.1:p.Thr1611Ile missense NM_001407933.1:c.4832C>T NP_001394862.1:p.Thr1611Ile missense NM_001407934.1:c.4829C>T NP_001394863.1:p.Thr1610Ile missense NM_001407935.1:c.4829C>T NP_001394864.1:p.Thr1610Ile missense NM_001407936.1:c.4829C>T NP_001394865.1:p.Thr1610Ile missense NM_001407937.1:c.4976C>T NP_001394866.1:p.Thr1659Ile missense NM_001407938.1:c.4976C>T NP_001394867.1:p.Thr1659Ile missense NM_001407939.1:c.4973C>T NP_001394868.1:p.Thr1658Ile missense NM_001407940.1:c.4973C>T NP_001394869.1:p.Thr1658Ile missense NM_001407941.1:c.4970C>T NP_001394870.1:p.Thr1657Ile missense NM_001407942.1:c.4958C>T NP_001394871.1:p.Thr1653Ile missense NM_001407943.1:c.4955C>T NP_001394872.1:p.Thr1652Ile missense NM_001407944.1:c.4955C>T NP_001394873.1:p.Thr1652Ile missense NM_001407945.1:c.4955C>T NP_001394874.1:p.Thr1652Ile missense NM_001407946.1:c.4766C>T NP_001394875.1:p.Thr1589Ile missense NM_001407947.1:c.4766C>T NP_001394876.1:p.Thr1589Ile missense NM_001407948.1:c.4766C>T NP_001394877.1:p.Thr1589Ile missense NM_001407949.1:c.4766C>T NP_001394878.1:p.Thr1589Ile missense NM_001407950.1:c.4763C>T NP_001394879.1:p.Thr1588Ile missense NM_001407951.1:c.4763C>T NP_001394880.1:p.Thr1588Ile missense NM_001407952.1:c.4763C>T NP_001394881.1:p.Thr1588Ile missense NM_001407953.1:c.4763C>T NP_001394882.1:p.Thr1588Ile missense NM_001407954.1:c.4763C>T NP_001394883.1:p.Thr1588Ile missense NM_001407955.1:c.4763C>T NP_001394884.1:p.Thr1588Ile missense NM_001407956.1:c.4760C>T NP_001394885.1:p.Thr1587Ile missense NM_001407957.1:c.4760C>T NP_001394886.1:p.Thr1587Ile missense NM_001407958.1:c.4760C>T NP_001394887.1:p.Thr1587Ile missense NM_001407959.1:c.4718C>T NP_001394888.1:p.Thr1573Ile missense NM_001407960.1:c.4715C>T NP_001394889.1:p.Thr1572Ile missense NM_001407962.1:c.4715C>T NP_001394891.1:p.Thr1572Ile missense NM_001407963.1:c.4712C>T NP_001394892.1:p.Thr1571Ile missense NM_001407964.1:c.4637C>T NP_001394893.1:p.Thr1546Ile missense NM_001407965.1:c.4592C>T NP_001394894.1:p.Thr1531Ile missense NM_001407966.1:c.4211C>T NP_001394895.1:p.Thr1404Ile missense NM_001407967.1:c.4208C>T NP_001394896.1:p.Thr1403Ile missense NM_001407968.1:c.2495C>T NP_001394897.1:p.Thr832Ile missense NM_001407969.1:c.2492C>T NP_001394898.1:p.Thr831Ile missense NM_001407970.1:c.1856C>T NP_001394899.1:p.Thr619Ile missense NM_001407971.1:c.1856C>T NP_001394900.1:p.Thr619Ile missense NM_001407972.1:c.1853C>T NP_001394901.1:p.Thr618Ile missense NM_001407973.1:c.1790C>T NP_001394902.1:p.Thr597Ile missense NM_001407974.1:c.1790C>T NP_001394903.1:p.Thr597Ile missense NM_001407975.1:c.1790C>T NP_001394904.1:p.Thr597Ile missense NM_001407976.1:c.1790C>T NP_001394905.1:p.Thr597Ile missense NM_001407977.1:c.1790C>T NP_001394906.1:p.Thr597Ile missense NM_001407978.1:c.1790C>T NP_001394907.1:p.Thr597Ile missense NM_001407979.1:c.1787C>T NP_001394908.1:p.Thr596Ile missense NM_001407980.1:c.1787C>T NP_001394909.1:p.Thr596Ile missense NM_001407981.1:c.1787C>T NP_001394910.1:p.Thr596Ile missense NM_001407982.1:c.1787C>T NP_001394911.1:p.Thr596Ile missense NM_001407983.1:c.1787C>T NP_001394912.1:p.Thr596Ile missense NM_001407984.1:c.1787C>T NP_001394913.1:p.Thr596Ile missense NM_001407985.1:c.1787C>T NP_001394914.1:p.Thr596Ile missense NM_001407986.1:c.1787C>T NP_001394915.1:p.Thr596Ile missense NM_001407990.1:c.1787C>T NP_001394919.1:p.Thr596Ile missense NM_001407991.1:c.1787C>T NP_001394920.1:p.Thr596Ile missense NM_001407992.1:c.1787C>T NP_001394921.1:p.Thr596Ile missense NM_001407993.1:c.1787C>T NP_001394922.1:p.Thr596Ile missense NM_001408392.1:c.1784C>T NP_001395321.1:p.Thr595Ile missense NM_001408396.1:c.1784C>T NP_001395325.1:p.Thr595Ile missense NM_001408397.1:c.1784C>T NP_001395326.1:p.Thr595Ile missense NM_001408398.1:c.1784C>T NP_001395327.1:p.Thr595Ile missense NM_001408399.1:c.1784C>T NP_001395328.1:p.Thr595Ile missense NM_001408400.1:c.1784C>T NP_001395329.1:p.Thr595Ile missense NM_001408401.1:c.1784C>T NP_001395330.1:p.Thr595Ile missense NM_001408402.1:c.1784C>T NP_001395331.1:p.Thr595Ile missense NM_001408403.1:c.1784C>T NP_001395332.1:p.Thr595Ile missense NM_001408404.1:c.1784C>T NP_001395333.1:p.Thr595Ile missense NM_001408406.1:c.1781C>T NP_001395335.1:p.Thr594Ile missense NM_001408407.1:c.1781C>T NP_001395336.1:p.Thr594Ile missense NM_001408408.1:c.1781C>T NP_001395337.1:p.Thr594Ile missense NM_001408409.1:c.1778C>T NP_001395338.1:p.Thr593Ile missense NM_001408410.1:c.1715C>T NP_001395339.1:p.Thr572Ile missense NM_001408411.1:c.1712C>T NP_001395340.1:p.Thr571Ile missense NM_001408412.1:c.1709C>T NP_001395341.1:p.Thr570Ile missense NM_001408413.1:c.1709C>T NP_001395342.1:p.Thr570Ile missense NM_001408414.1:c.1709C>T NP_001395343.1:p.Thr570Ile missense NM_001408415.1:c.1709C>T NP_001395344.1:p.Thr570Ile missense NM_001408416.1:c.1709C>T NP_001395345.1:p.Thr570Ile missense NM_001408418.1:c.1673C>T NP_001395347.1:p.Thr558Ile missense NM_001408419.1:c.1673C>T NP_001395348.1:p.Thr558Ile missense NM_001408420.1:c.1673C>T NP_001395349.1:p.Thr558Ile missense NM_001408421.1:c.1670C>T NP_001395350.1:p.Thr557Ile missense NM_001408422.1:c.1670C>T NP_001395351.1:p.Thr557Ile missense NM_001408423.1:c.1670C>T NP_001395352.1:p.Thr557Ile missense NM_001408424.1:c.1670C>T NP_001395353.1:p.Thr557Ile missense NM_001408425.1:c.1667C>T NP_001395354.1:p.Thr556Ile missense NM_001408426.1:c.1667C>T NP_001395355.1:p.Thr556Ile missense NM_001408427.1:c.1667C>T NP_001395356.1:p.Thr556Ile missense NM_001408428.1:c.1667C>T NP_001395357.1:p.Thr556Ile missense NM_001408429.1:c.1667C>T NP_001395358.1:p.Thr556Ile missense NM_001408430.1:c.1667C>T NP_001395359.1:p.Thr556Ile missense NM_001408431.1:c.1667C>T NP_001395360.1:p.Thr556Ile missense NM_001408432.1:c.1664C>T NP_001395361.1:p.Thr555Ile missense NM_001408433.1:c.1664C>T NP_001395362.1:p.Thr555Ile missense NM_001408434.1:c.1664C>T NP_001395363.1:p.Thr555Ile missense NM_001408435.1:c.1664C>T NP_001395364.1:p.Thr555Ile missense NM_001408436.1:c.1664C>T NP_001395365.1:p.Thr555Ile missense NM_001408437.1:c.1664C>T NP_001395366.1:p.Thr555Ile missense NM_001408438.1:c.1664C>T NP_001395367.1:p.Thr555Ile missense NM_001408439.1:c.1664C>T NP_001395368.1:p.Thr555Ile missense NM_001408440.1:c.1664C>T NP_001395369.1:p.Thr555Ile missense NM_001408441.1:c.1664C>T NP_001395370.1:p.Thr555Ile missense NM_001408442.1:c.1664C>T NP_001395371.1:p.Thr555Ile missense NM_001408443.1:c.1664C>T NP_001395372.1:p.Thr555Ile missense NM_001408444.1:c.1664C>T NP_001395373.1:p.Thr555Ile missense NM_001408445.1:c.1661C>T NP_001395374.1:p.Thr554Ile missense NM_001408446.1:c.1661C>T NP_001395375.1:p.Thr554Ile missense NM_001408447.1:c.1661C>T NP_001395376.1:p.Thr554Ile missense NM_001408448.1:c.1661C>T NP_001395377.1:p.Thr554Ile missense NM_001408450.1:c.1661C>T NP_001395379.1:p.Thr554Ile missense NM_001408451.1:c.1655C>T NP_001395380.1:p.Thr552Ile missense NM_001408452.1:c.1649C>T NP_001395381.1:p.Thr550Ile missense NM_001408453.1:c.1649C>T NP_001395382.1:p.Thr550Ile missense NM_001408454.1:c.1649C>T NP_001395383.1:p.Thr550Ile missense NM_001408455.1:c.1649C>T NP_001395384.1:p.Thr550Ile missense NM_001408456.1:c.1649C>T NP_001395385.1:p.Thr550Ile missense NM_001408457.1:c.1649C>T NP_001395386.1:p.Thr550Ile missense NM_001408458.1:c.1646C>T NP_001395387.1:p.Thr549Ile missense NM_001408459.1:c.1646C>T NP_001395388.1:p.Thr549Ile missense NM_001408460.1:c.1646C>T NP_001395389.1:p.Thr549Ile missense NM_001408461.1:c.1646C>T NP_001395390.1:p.Thr549Ile missense NM_001408462.1:c.1646C>T NP_001395391.1:p.Thr549Ile missense NM_001408463.1:c.1646C>T NP_001395392.1:p.Thr549Ile missense NM_001408464.1:c.1646C>T NP_001395393.1:p.Thr549Ile missense NM_001408465.1:c.1646C>T NP_001395394.1:p.Thr549Ile missense NM_001408466.1:c.1646C>T NP_001395395.1:p.Thr549Ile missense NM_001408467.1:c.1646C>T NP_001395396.1:p.Thr549Ile missense NM_001408468.1:c.1643C>T NP_001395397.1:p.Thr548Ile missense NM_001408469.1:c.1643C>T NP_001395398.1:p.Thr548Ile missense NM_001408470.1:c.1643C>T NP_001395399.1:p.Thr548Ile missense NM_001408472.1:c.1787C>T NP_001395401.1:p.Thr596Ile missense NM_001408473.1:c.1784C>T NP_001395402.1:p.Thr595Ile missense NM_001408474.1:c.1589C>T NP_001395403.1:p.Thr530Ile missense NM_001408475.1:c.1586C>T NP_001395404.1:p.Thr529Ile missense NM_001408476.1:c.1586C>T NP_001395405.1:p.Thr529Ile missense NM_001408478.1:c.1580C>T NP_001395407.1:p.Thr527Ile missense NM_001408479.1:c.1580C>T NP_001395408.1:p.Thr527Ile missense NM_001408480.1:c.1580C>T NP_001395409.1:p.Thr527Ile missense NM_001408481.1:c.1577C>T NP_001395410.1:p.Thr526Ile missense NM_001408482.1:c.1577C>T NP_001395411.1:p.Thr526Ile missense NM_001408483.1:c.1577C>T NP_001395412.1:p.Thr526Ile missense NM_001408484.1:c.1577C>T NP_001395413.1:p.Thr526Ile missense NM_001408485.1:c.1577C>T NP_001395414.1:p.Thr526Ile missense NM_001408489.1:c.1577C>T NP_001395418.1:p.Thr526Ile missense NM_001408490.1:c.1577C>T NP_001395419.1:p.Thr526Ile missense NM_001408491.1:c.1577C>T NP_001395420.1:p.Thr526Ile missense NM_001408492.1:c.1574C>T NP_001395421.1:p.Thr525Ile missense NM_001408493.1:c.1574C>T NP_001395422.1:p.Thr525Ile missense NM_001408494.1:c.1550C>T NP_001395423.1:p.Thr517Ile missense NM_001408495.1:c.1544C>T NP_001395424.1:p.Thr515Ile missense NM_001408496.1:c.1526C>T NP_001395425.1:p.Thr509Ile missense NM_001408497.1:c.1526C>T NP_001395426.1:p.Thr509Ile missense NM_001408498.1:c.1526C>T NP_001395427.1:p.Thr509Ile missense NM_001408499.1:c.1526C>T NP_001395428.1:p.Thr509Ile missense NM_001408500.1:c.1526C>T NP_001395429.1:p.Thr509Ile missense NM_001408501.1:c.1526C>T NP_001395430.1:p.Thr509Ile missense NM_001408502.1:c.1523C>T NP_001395431.1:p.Thr508Ile missense NM_001408503.1:c.1523C>T NP_001395432.1:p.Thr508Ile missense NM_001408504.1:c.1523C>T NP_001395433.1:p.Thr508Ile missense NM_001408505.1:c.1520C>T NP_001395434.1:p.Thr507Ile missense NM_001408506.1:c.1463C>T NP_001395435.1:p.Thr488Ile missense NM_001408507.1:c.1460C>T NP_001395436.1:p.Thr487Ile missense NM_001408508.1:c.1451C>T NP_001395437.1:p.Thr484Ile missense NM_001408509.1:c.1448C>T NP_001395438.1:p.Thr483Ile missense NM_001408510.1:c.1409C>T NP_001395439.1:p.Thr470Ile missense NM_001408511.1:c.1406C>T NP_001395440.1:p.Thr469Ile missense NM_001408512.1:c.1286C>T NP_001395441.1:p.Thr429Ile missense NM_001408513.1:c.1259C>T NP_001395442.1:p.Thr420Ile missense NM_001408514.1:c.863C>T NP_001395443.1:p.Thr288Ile missense NM_007297.4:c.4958C>T NP_009228.2:p.Thr1653Ile missense NM_007298.4:c.1787C>T NP_009229.2:p.Thr596Ile missense NM_007299.4:c.1787C>T NP_009230.2:p.Thr596Ile missense NM_007300.4:c.5162C>T NP_009231.2:p.Thr1721Ile missense NM_007304.2:c.1787C>T NP_009235.2:p.Thr596Ile missense NR_027676.2:n.5276C>T non-coding transcript variant NC_000017.11:g.43063927G>A NC_000017.10:g.41215944G>A NG_005905.2:g.154057C>T LRG_292:g.154057C>T LRG_292t1:c.5099C>T LRG_292p1:p.Thr1700Ile - Protein change
- T1721I, T1653I, T596I, T1700I, T1531I, T1546I, T1571I, T1573I, T1587I, T1612I, T1658I, T1696I, T1697I, T1699I, T483I, T484I, T507I, T515I, T530I, T552I, T556I, T594I, T597I, T1588I, T1589I, T1628I, T1633I, T1652I, T1657I, T1659I, T1672I, T1673I, T1680I, T1695I, T1698I, T1720I, T288I, T525I, T549I, T558I, T593I, T1404I, T1572I, T1611I, T1631I, T1651I, T420I, T429I, T470I, T488I, T509I, T526I, T529I, T550I, T555I, T570I, T595I, T618I, T619I, T1403I, T1610I, T1629I, T1630I, T1656I, T1674I, T1681I, T1722I, T469I, T487I, T508I, T517I, T527I, T548I, T554I, T557I, T571I, T572I, T831I, T832I
- Other names
- -
- Canonical SPDI
- NC_000017.11:43063926:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
functionally_abnormal; Sequence Ontology [ SO:0002218]The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5099C>T, a MISSENSE variant, produced a function score of -2.49, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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. |
|---|---|---|---|---|
| not provided (1) |
no classification provided
|
- | RCV001072251.3 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Nov 5, 2020 | RCV002348494.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Nov 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002645783.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.T1700I variant (also known as c.5099C>T), located in coding exon 16 of the BRCA1 gene, results from a C to T substitution at nucleotide … (more)
The p.T1700I variant (also known as c.5099C>T), located in coding exon 16 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5099. The threonine at codon 1700 is replaced by isoleucine, an amino acid with similar properties. One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Another functional assay determined this alteration to be deficient in homologous recombination repair activity (Petitalot A et al. Mol Cancer Res, 2019 01;17:54-69). Based on internal structural analysis, this variant is anticipated to disrupt a region of known function (Ambry internal data; Wu Q et al. Mol Cell 2016 Feb;61(3):434-448; Tram E et al. PLoS One 2013 May;8(5):e62468). Another alteration at the same codon, p.T1700A (c.5098A>G), has also been determined to be functionally and structurally deleterious (Ambry internal data; Findlay GM et al. Nature, 2018 10;562:217-222; Wu Q et al. Mol Cell 2016 Feb;61(3):434-448; Tram E et al. PLoS One 2013 May;8(5):e62468). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001237597.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-2.4917463603023
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Comment:
Germline Functional Evidence
| Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001237597.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5099C>T, a MISSENSE variant, produced a function score of -2.49, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5099C>T, a MISSENSE variant, produced a function score of -2.49, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Comment:
The p.T1700I variant (also known as c.5099C>T), located in coding exon 16 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5099. The threonine at codon 1700 is replaced by isoleucine, an amino acid with similar properties. One functional study found that this nucleotide substitution is deleterious in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222). Another functional assay determined this alteration to be deficient in homologous recombination repair activity (Petitalot A et al. Mol Cancer Res, 2019 01;17:54-69). Based on internal structural analysis, this variant is anticipated to disrupt a region of known function (Ambry internal data; Wu Q et al. Mol Cell 2016 Feb;61(3):434-448; Tram E et al. PLoS One 2013 May;8(5):e62468). Another alteration at the same codon, p.T1700A (c.5098A>G), has also been determined to be functionally and structurally deleterious (Ambry internal data; Findlay GM et al. Nature, 2018 10;562:217-222; Wu Q et al. Mol Cell 2016 Feb;61(3):434-448; Tram E et al. PLoS One 2013 May;8(5):e62468). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk. | Petitalot A | Molecular cancer research : MCR | 2019 | PMID: 30257991 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea. | Ryu JM | Breast (Edinburgh, Scotland) | 2017 | PMID: 28364669 |
| Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites. | Wu Q | Molecular cell | 2016 | PMID: 26778126 |
| Missense variants of uncertain significance (VUS) altering the phosphorylation patterns of BRCA1 and BRCA2. | Tram E | PloS one | 2013 | PMID: 23704879 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
Text-mined citations for rs2051927197 ...
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 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.