VCV000054131.16 - ClinVar

NM_007294.4(BRCA1):c.110C>A (p.Thr37Lys)

Germline

Top reviewed classifications are shown here.

Submission summary:

7 submissions

7 submitters

4 conditions

Reviewed by expert panel

Pathogenic

Aug 2015 by Evidence-based…

for Breast-ovarian cancer, familial 1

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.110C>A (p.Thr37Lys)

Variation ID: 54131 Accession: VCV000054131.16

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43115750 (GRCh38) [ NCBI UCSC ] 17: 41267767 (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	Apr 1, 2014	May 1, 2024	Aug 10, 2015

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.110C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.Thr37Lys	missense
NM_001407571.1:c.-79C>A
NM_001407581.1:c.110C>A	NP_001394510.1:p.Thr37Lys	missense
NM_001407582.1:c.110C>A	NP_001394511.1:p.Thr37Lys	missense
NM_001407583.1:c.110C>A	NP_001394512.1:p.Thr37Lys	missense
NM_001407585.1:c.110C>A	NP_001394514.1:p.Thr37Lys	missense
NM_001407587.1:c.110C>A	NP_001394516.1:p.Thr37Lys	missense
NM_001407590.1:c.110C>A	NP_001394519.1:p.Thr37Lys	missense
NM_001407591.1:c.110C>A	NP_001394520.1:p.Thr37Lys	missense
NM_001407593.1:c.110C>A	NP_001394522.1:p.Thr37Lys	missense
NM_001407594.1:c.110C>A	NP_001394523.1:p.Thr37Lys	missense
NM_001407596.1:c.110C>A	NP_001394525.1:p.Thr37Lys	missense
NM_001407597.1:c.110C>A	NP_001394526.1:p.Thr37Lys	missense
NM_001407598.1:c.110C>A	NP_001394527.1:p.Thr37Lys	missense
NM_001407602.1:c.110C>A	NP_001394531.1:p.Thr37Lys	missense
NM_001407603.1:c.110C>A	NP_001394532.1:p.Thr37Lys	missense
NM_001407605.1:c.110C>A	NP_001394534.1:p.Thr37Lys	missense
NM_001407610.1:c.110C>A	NP_001394539.1:p.Thr37Lys	missense
NM_001407611.1:c.110C>A	NP_001394540.1:p.Thr37Lys	missense
NM_001407612.1:c.110C>A	NP_001394541.1:p.Thr37Lys	missense
NM_001407613.1:c.110C>A	NP_001394542.1:p.Thr37Lys	missense
NM_001407614.1:c.110C>A	NP_001394543.1:p.Thr37Lys	missense
NM_001407615.1:c.110C>A	NP_001394544.1:p.Thr37Lys	missense
NM_001407616.1:c.110C>A	NP_001394545.1:p.Thr37Lys	missense
NM_001407617.1:c.110C>A	NP_001394546.1:p.Thr37Lys	missense
NM_001407618.1:c.110C>A	NP_001394547.1:p.Thr37Lys	missense
NM_001407619.1:c.110C>A	NP_001394548.1:p.Thr37Lys	missense
NM_001407620.1:c.110C>A	NP_001394549.1:p.Thr37Lys	missense
NM_001407621.1:c.110C>A	NP_001394550.1:p.Thr37Lys	missense
NM_001407622.1:c.110C>A	NP_001394551.1:p.Thr37Lys	missense
NM_001407623.1:c.110C>A	NP_001394552.1:p.Thr37Lys	missense
NM_001407624.1:c.110C>A	NP_001394553.1:p.Thr37Lys	missense
NM_001407625.1:c.110C>A	NP_001394554.1:p.Thr37Lys	missense
NM_001407626.1:c.110C>A	NP_001394555.1:p.Thr37Lys	missense
NM_001407627.1:c.110C>A	NP_001394556.1:p.Thr37Lys	missense
NM_001407628.1:c.110C>A	NP_001394557.1:p.Thr37Lys	missense
NM_001407629.1:c.110C>A	NP_001394558.1:p.Thr37Lys	missense
NM_001407630.1:c.110C>A	NP_001394559.1:p.Thr37Lys	missense
NM_001407631.1:c.110C>A	NP_001394560.1:p.Thr37Lys	missense
NM_001407632.1:c.110C>A	NP_001394561.1:p.Thr37Lys	missense
NM_001407633.1:c.110C>A	NP_001394562.1:p.Thr37Lys	missense
NM_001407634.1:c.110C>A	NP_001394563.1:p.Thr37Lys	missense
NM_001407635.1:c.110C>A	NP_001394564.1:p.Thr37Lys	missense
NM_001407636.1:c.110C>A	NP_001394565.1:p.Thr37Lys	missense
NM_001407637.1:c.110C>A	NP_001394566.1:p.Thr37Lys	missense
NM_001407638.1:c.110C>A	NP_001394567.1:p.Thr37Lys	missense
NM_001407639.1:c.110C>A	NP_001394568.1:p.Thr37Lys	missense
NM_001407640.1:c.110C>A	NP_001394569.1:p.Thr37Lys	missense
NM_001407641.1:c.110C>A	NP_001394570.1:p.Thr37Lys	missense
NM_001407642.1:c.110C>A	NP_001394571.1:p.Thr37Lys	missense
NM_001407644.1:c.110C>A	NP_001394573.1:p.Thr37Lys	missense
NM_001407645.1:c.110C>A	NP_001394574.1:p.Thr37Lys	missense
NM_001407646.1:c.110C>A	NP_001394575.1:p.Thr37Lys	missense
NM_001407647.1:c.110C>A	NP_001394576.1:p.Thr37Lys	missense
NM_001407648.1:c.110C>A	NP_001394577.1:p.Thr37Lys	missense
NM_001407649.1:c.110C>A	NP_001394578.1:p.Thr37Lys	missense
NM_001407652.1:c.110C>A	NP_001394581.1:p.Thr37Lys	missense
NM_001407653.1:c.110C>A	NP_001394582.1:p.Thr37Lys	missense
NM_001407654.1:c.110C>A	NP_001394583.1:p.Thr37Lys	missense
NM_001407655.1:c.110C>A	NP_001394584.1:p.Thr37Lys	missense
NM_001407656.1:c.110C>A	NP_001394585.1:p.Thr37Lys	missense
NM_001407657.1:c.110C>A	NP_001394586.1:p.Thr37Lys	missense
NM_001407658.1:c.110C>A	NP_001394587.1:p.Thr37Lys	missense
NM_001407659.1:c.110C>A	NP_001394588.1:p.Thr37Lys	missense
NM_001407660.1:c.110C>A	NP_001394589.1:p.Thr37Lys	missense
NM_001407661.1:c.110C>A	NP_001394590.1:p.Thr37Lys	missense
NM_001407662.1:c.110C>A	NP_001394591.1:p.Thr37Lys	missense
NM_001407663.1:c.110C>A	NP_001394592.1:p.Thr37Lys	missense
NM_001407664.1:c.110C>A	NP_001394593.1:p.Thr37Lys	missense
NM_001407665.1:c.110C>A	NP_001394594.1:p.Thr37Lys	missense
NM_001407666.1:c.110C>A	NP_001394595.1:p.Thr37Lys	missense
NM_001407667.1:c.110C>A	NP_001394596.1:p.Thr37Lys	missense
NM_001407668.1:c.110C>A	NP_001394597.1:p.Thr37Lys	missense
NM_001407669.1:c.110C>A	NP_001394598.1:p.Thr37Lys	missense
NM_001407670.1:c.110C>A	NP_001394599.1:p.Thr37Lys	missense
NM_001407671.1:c.110C>A	NP_001394600.1:p.Thr37Lys	missense
NM_001407672.1:c.110C>A	NP_001394601.1:p.Thr37Lys	missense
NM_001407673.1:c.110C>A	NP_001394602.1:p.Thr37Lys	missense
NM_001407674.1:c.110C>A	NP_001394603.1:p.Thr37Lys	missense
NM_001407675.1:c.110C>A	NP_001394604.1:p.Thr37Lys	missense
NM_001407676.1:c.110C>A	NP_001394605.1:p.Thr37Lys	missense
NM_001407677.1:c.110C>A	NP_001394606.1:p.Thr37Lys	missense
NM_001407678.1:c.110C>A	NP_001394607.1:p.Thr37Lys	missense
NM_001407679.1:c.110C>A	NP_001394608.1:p.Thr37Lys	missense
NM_001407680.1:c.110C>A	NP_001394609.1:p.Thr37Lys	missense
NM_001407681.1:c.110C>A	NP_001394610.1:p.Thr37Lys	missense
NM_001407682.1:c.110C>A	NP_001394611.1:p.Thr37Lys	missense
NM_001407683.1:c.110C>A	NP_001394612.1:p.Thr37Lys	missense
NM_001407684.1:c.110C>A	NP_001394613.1:p.Thr37Lys	missense
NM_001407685.1:c.110C>A	NP_001394614.1:p.Thr37Lys	missense
NM_001407686.1:c.110C>A	NP_001394615.1:p.Thr37Lys	missense
NM_001407687.1:c.110C>A	NP_001394616.1:p.Thr37Lys	missense
NM_001407688.1:c.110C>A	NP_001394617.1:p.Thr37Lys	missense
NM_001407689.1:c.110C>A	NP_001394618.1:p.Thr37Lys	missense
NM_001407690.1:c.110C>A	NP_001394619.1:p.Thr37Lys	missense
NM_001407691.1:c.110C>A	NP_001394620.1:p.Thr37Lys	missense
NM_001407694.1:c.-148C>A
NM_001407695.1:c.-152C>A
NM_001407696.1:c.-148C>A
NM_001407697.1:c.-32C>A
NM_001407724.1:c.-148C>A
NM_001407725.1:c.-32C>A
NM_001407727.1:c.-148C>A
NM_001407728.1:c.-32C>A
NM_001407729.1:c.-32C>A
NM_001407730.1:c.-32C>A
NM_001407731.1:c.-148C>A
NM_001407733.1:c.-148C>A
NM_001407734.1:c.-32C>A
NM_001407735.1:c.-32C>A
NM_001407737.1:c.-32C>A
NM_001407739.1:c.-32C>A
NM_001407740.1:c.-32C>A
NM_001407741.1:c.-32C>A
NM_001407743.1:c.-32C>A
NM_001407745.1:c.-32C>A
NM_001407746.1:c.-148C>A
NM_001407748.1:c.-32C>A
NM_001407749.1:c.-148C>A
NM_001407752.1:c.-32C>A
NM_001407838.1:c.-32C>A
NM_001407839.1:c.-32C>A
NM_001407841.1:c.-28C>A
NM_001407842.1:c.-148C>A
NM_001407843.1:c.-148C>A
NM_001407844.1:c.-32C>A
NM_001407846.1:c.-32C>A
NM_001407847.1:c.-32C>A
NM_001407848.1:c.-32C>A
NM_001407850.1:c.-32C>A
NM_001407851.1:c.-32C>A
NM_001407853.1:c.-79C>A
NM_001407854.1:c.110C>A	NP_001394783.1:p.Thr37Lys	missense
NM_001407858.1:c.110C>A	NP_001394787.1:p.Thr37Lys	missense
NM_001407859.1:c.110C>A	NP_001394788.1:p.Thr37Lys	missense
NM_001407860.1:c.110C>A	NP_001394789.1:p.Thr37Lys	missense
NM_001407861.1:c.110C>A	NP_001394790.1:p.Thr37Lys	missense
NM_001407862.1:c.110C>A	NP_001394791.1:p.Thr37Lys	missense
NM_001407863.1:c.110C>A	NP_001394792.1:p.Thr37Lys	missense
NM_001407874.1:c.110C>A	NP_001394803.1:p.Thr37Lys	missense
NM_001407875.1:c.110C>A	NP_001394804.1:p.Thr37Lys	missense
NM_001407879.1:c.-79C>A
NM_001407882.1:c.-79C>A
NM_001407884.1:c.-79C>A
NM_001407885.1:c.-79C>A
NM_001407886.1:c.-79C>A
NM_001407887.1:c.-79C>A
NM_001407889.1:c.-195C>A
NM_001407894.1:c.-79C>A
NM_001407895.1:c.-79C>A
NM_001407896.1:c.-79C>A
NM_001407897.1:c.-79C>A
NM_001407899.1:c.-79C>A
NM_001407900.1:c.-195C>A
NM_001407904.1:c.-79C>A
NM_001407906.1:c.-79C>A
NM_001407907.1:c.-79C>A
NM_001407908.1:c.-79C>A
NM_001407909.1:c.-79C>A
NM_001407910.1:c.-79C>A
NM_001407915.1:c.-79C>A
NM_001407916.1:c.-79C>A
NM_001407917.1:c.-79C>A
NM_001407918.1:c.-79C>A
NM_001407919.1:c.110C>A	NP_001394848.1:p.Thr37Lys	missense
NM_001407920.1:c.-32C>A
NM_001407921.1:c.-32C>A
NM_001407922.1:c.-32C>A
NM_001407923.1:c.-32C>A
NM_001407926.1:c.-32C>A
NM_001407927.1:c.-32C>A
NM_001407930.1:c.-148C>A
NM_001407933.1:c.-32C>A
NM_001407934.1:c.-32C>A
NM_001407935.1:c.-32C>A
NM_001407937.1:c.110C>A	NP_001394866.1:p.Thr37Lys	missense
NM_001407938.1:c.110C>A	NP_001394867.1:p.Thr37Lys	missense
NM_001407939.1:c.110C>A	NP_001394868.1:p.Thr37Lys	missense
NM_001407940.1:c.110C>A	NP_001394869.1:p.Thr37Lys	missense
NM_001407941.1:c.110C>A	NP_001394870.1:p.Thr37Lys	missense
NM_001407942.1:c.-148C>A
NM_001407943.1:c.-32C>A
NM_001407944.1:c.-32C>A
NM_001407946.1:c.-79C>A
NM_001407947.1:c.-79C>A
NM_001407948.1:c.-79C>A
NM_001407949.1:c.-79C>A
NM_001407950.1:c.-79C>A
NM_001407951.1:c.-79C>A
NM_001407952.1:c.-79C>A
NM_001407953.1:c.-79C>A
NM_001407954.1:c.-79C>A
NM_001407955.1:c.-79C>A
NM_001407956.1:c.-79C>A
NM_001407957.1:c.-79C>A
NM_001407958.1:c.-79C>A
NM_001407960.1:c.-194C>A
NM_001407962.1:c.-194C>A
NM_001407964.1:c.-32C>A
NM_001407965.1:c.-310C>A
NM_001407968.1:c.110C>A	NP_001394897.1:p.Thr37Lys	missense
NM_001407969.1:c.110C>A	NP_001394898.1:p.Thr37Lys	missense
NM_001407970.1:c.110C>A	NP_001394899.1:p.Thr37Lys	missense
NM_001407971.1:c.110C>A	NP_001394900.1:p.Thr37Lys	missense
NM_001407972.1:c.110C>A	NP_001394901.1:p.Thr37Lys	missense
NM_001407973.1:c.110C>A	NP_001394902.1:p.Thr37Lys	missense
NM_001407974.1:c.110C>A	NP_001394903.1:p.Thr37Lys	missense
NM_001407975.1:c.110C>A	NP_001394904.1:p.Thr37Lys	missense
NM_001407976.1:c.110C>A	NP_001394905.1:p.Thr37Lys	missense
NM_001407977.1:c.110C>A	NP_001394906.1:p.Thr37Lys	missense
NM_001407978.1:c.110C>A	NP_001394907.1:p.Thr37Lys	missense
NM_001407979.1:c.110C>A	NP_001394908.1:p.Thr37Lys	missense
NM_001407980.1:c.110C>A	NP_001394909.1:p.Thr37Lys	missense
NM_001407981.1:c.110C>A	NP_001394910.1:p.Thr37Lys	missense
NM_001407982.1:c.110C>A	NP_001394911.1:p.Thr37Lys	missense
NM_001407983.1:c.110C>A	NP_001394912.1:p.Thr37Lys	missense
NM_001407984.1:c.110C>A	NP_001394913.1:p.Thr37Lys	missense
NM_001407985.1:c.110C>A	NP_001394914.1:p.Thr37Lys	missense
NM_001407986.1:c.110C>A	NP_001394915.1:p.Thr37Lys	missense
NM_001407990.1:c.110C>A	NP_001394919.1:p.Thr37Lys	missense
NM_001407991.1:c.110C>A	NP_001394920.1:p.Thr37Lys	missense
NM_001407992.1:c.110C>A	NP_001394921.1:p.Thr37Lys	missense
NM_001407993.1:c.110C>A	NP_001394922.1:p.Thr37Lys	missense
NM_001408392.1:c.110C>A	NP_001395321.1:p.Thr37Lys	missense
NM_001408396.1:c.110C>A	NP_001395325.1:p.Thr37Lys	missense
NM_001408397.1:c.110C>A	NP_001395326.1:p.Thr37Lys	missense
NM_001408398.1:c.110C>A	NP_001395327.1:p.Thr37Lys	missense
NM_001408399.1:c.110C>A	NP_001395328.1:p.Thr37Lys	missense
NM_001408400.1:c.110C>A	NP_001395329.1:p.Thr37Lys	missense
NM_001408401.1:c.110C>A	NP_001395330.1:p.Thr37Lys	missense
NM_001408402.1:c.110C>A	NP_001395331.1:p.Thr37Lys	missense
NM_001408403.1:c.110C>A	NP_001395332.1:p.Thr37Lys	missense
NM_001408404.1:c.110C>A	NP_001395333.1:p.Thr37Lys	missense
NM_001408406.1:c.110C>A	NP_001395335.1:p.Thr37Lys	missense
NM_001408407.1:c.110C>A	NP_001395336.1:p.Thr37Lys	missense
NM_001408408.1:c.110C>A	NP_001395337.1:p.Thr37Lys	missense
NM_001408409.1:c.110C>A	NP_001395338.1:p.Thr37Lys	missense
NM_001408410.1:c.-32C>A
NM_001408411.1:c.110C>A	NP_001395340.1:p.Thr37Lys	missense
NM_001408412.1:c.110C>A	NP_001395341.1:p.Thr37Lys	missense
NM_001408413.1:c.110C>A	NP_001395342.1:p.Thr37Lys	missense
NM_001408414.1:c.110C>A	NP_001395343.1:p.Thr37Lys	missense
NM_001408415.1:c.110C>A	NP_001395344.1:p.Thr37Lys	missense
NM_001408416.1:c.110C>A	NP_001395345.1:p.Thr37Lys	missense
NM_001408418.1:c.110C>A	NP_001395347.1:p.Thr37Lys	missense
NM_001408419.1:c.110C>A	NP_001395348.1:p.Thr37Lys	missense
NM_001408420.1:c.110C>A	NP_001395349.1:p.Thr37Lys	missense
NM_001408421.1:c.110C>A	NP_001395350.1:p.Thr37Lys	missense
NM_001408422.1:c.110C>A	NP_001395351.1:p.Thr37Lys	missense
NM_001408423.1:c.110C>A	NP_001395352.1:p.Thr37Lys	missense
NM_001408424.1:c.110C>A	NP_001395353.1:p.Thr37Lys	missense
NM_001408425.1:c.110C>A	NP_001395354.1:p.Thr37Lys	missense
NM_001408426.1:c.110C>A	NP_001395355.1:p.Thr37Lys	missense
NM_001408427.1:c.110C>A	NP_001395356.1:p.Thr37Lys	missense
NM_001408428.1:c.110C>A	NP_001395357.1:p.Thr37Lys	missense
NM_001408429.1:c.110C>A	NP_001395358.1:p.Thr37Lys	missense
NM_001408430.1:c.110C>A	NP_001395359.1:p.Thr37Lys	missense
NM_001408431.1:c.110C>A	NP_001395360.1:p.Thr37Lys	missense
NM_001408432.1:c.110C>A	NP_001395361.1:p.Thr37Lys	missense
NM_001408433.1:c.110C>A	NP_001395362.1:p.Thr37Lys	missense
NM_001408434.1:c.110C>A	NP_001395363.1:p.Thr37Lys	missense
NM_001408435.1:c.110C>A	NP_001395364.1:p.Thr37Lys	missense
NM_001408436.1:c.110C>A	NP_001395365.1:p.Thr37Lys	missense
NM_001408437.1:c.110C>A	NP_001395366.1:p.Thr37Lys	missense
NM_001408438.1:c.110C>A	NP_001395367.1:p.Thr37Lys	missense
NM_001408439.1:c.110C>A	NP_001395368.1:p.Thr37Lys	missense
NM_001408440.1:c.110C>A	NP_001395369.1:p.Thr37Lys	missense
NM_001408441.1:c.110C>A	NP_001395370.1:p.Thr37Lys	missense
NM_001408442.1:c.110C>A	NP_001395371.1:p.Thr37Lys	missense
NM_001408443.1:c.110C>A	NP_001395372.1:p.Thr37Lys	missense
NM_001408444.1:c.110C>A	NP_001395373.1:p.Thr37Lys	missense
NM_001408445.1:c.110C>A	NP_001395374.1:p.Thr37Lys	missense
NM_001408446.1:c.110C>A	NP_001395375.1:p.Thr37Lys	missense
NM_001408447.1:c.110C>A	NP_001395376.1:p.Thr37Lys	missense
NM_001408448.1:c.110C>A	NP_001395377.1:p.Thr37Lys	missense
NM_001408450.1:c.110C>A	NP_001395379.1:p.Thr37Lys	missense
NM_001408452.1:c.-32C>A
NM_001408453.1:c.-32C>A
NM_001408455.1:c.-148C>A
NM_001408456.1:c.-148C>A
NM_001408458.1:c.-32C>A
NM_001408462.1:c.-32C>A
NM_001408463.1:c.-32C>A
NM_001408465.1:c.-152C>A
NM_001408466.1:c.-32C>A
NM_001408468.1:c.-148C>A
NM_001408469.1:c.-32C>A
NM_001408470.1:c.-32C>A
NM_001408472.1:c.110C>A	NP_001395401.1:p.Thr37Lys	missense
NM_001408473.1:c.110C>A	NP_001395402.1:p.Thr37Lys	missense
NM_001408474.1:c.110C>A	NP_001395403.1:p.Thr37Lys	missense
NM_001408475.1:c.110C>A	NP_001395404.1:p.Thr37Lys	missense
NM_001408476.1:c.110C>A	NP_001395405.1:p.Thr37Lys	missense
NM_001408478.1:c.-79C>A
NM_001408479.1:c.-79C>A
NM_001408480.1:c.-79C>A
NM_001408481.1:c.-79C>A
NM_001408482.1:c.-79C>A
NM_001408483.1:c.-79C>A
NM_001408484.1:c.-79C>A
NM_001408485.1:c.-79C>A
NM_001408489.1:c.-79C>A
NM_001408490.1:c.-79C>A
NM_001408491.1:c.-79C>A
NM_001408492.1:c.-195C>A
NM_001408493.1:c.-79C>A
NM_001408494.1:c.110C>A	NP_001395423.1:p.Thr37Lys	missense
NM_001408495.1:c.110C>A	NP_001395424.1:p.Thr37Lys	missense
NM_001408497.1:c.-32C>A
NM_001408499.1:c.-32C>A
NM_001408500.1:c.-32C>A
NM_001408501.1:c.-148C>A
NM_001408502.1:c.-79C>A
NM_001408503.1:c.-32C>A
NM_001408504.1:c.-32C>A
NM_001408505.1:c.-32C>A
NM_001408506.1:c.-79C>A
NM_001408507.1:c.-79C>A
NM_001408508.1:c.-79C>A
NM_001408509.1:c.-79C>A
NM_001408510.1:c.-194C>A
NM_001408512.1:c.-194C>A
NM_001408513.1:c.-79C>A
NM_001408514.1:c.-79C>A
NM_007297.4:c.-8+8267C>A		intron variant
NM_007298.4:c.110C>A	NP_009229.2:p.Thr37Lys	missense
NM_007299.4:c.110C>A	NP_009230.2:p.Thr37Lys	missense
NM_007300.4:c.110C>A	NP_009231.2:p.Thr37Lys	missense
NM_007304.2:c.110C>A	NP_009235.2:p.Thr37Lys	missense
NR_027676.2:n.312C>A		non-coding transcript variant
NC_000017.11:g.43115750G>T
NC_000017.10:g.41267767G>T
NG_005905.2:g.102234C>A
LRG_292:g.102234C>A
LRG_292t1:c.110C>A	LRG_292p1:p.Thr37Lys
U14680.1:n.229C>A

... more HGVS ... less HGVS

Protein change

T37K

Other names

229C>A

Canonical SPDI

NC_000017.11:43115749:G:T

Functional consequence Help The 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.110C>A, 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: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, 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) Help The 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

BRCA1-HCI: BRCA1_00112 ClinGen: CA000742 dbSNP: rs80356880 VarSome

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
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BRCA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	13041	14847

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Breast-ovarian cancer, familial, susceptibility to, 1	Pathogenic (4)	reviewed by expert panel	Aug 10, 2015	RCV000111781.14
Breast-ovarian cancer, familial, susceptibility to, 1 Familial cancer of breast Fanconi anemia, complementation group S Pancreatic cancer, susceptibility to, 4	Pathogenic (1)	criteria provided, single submitter	Oct 31, 2018	RCV000763401.10
Hereditary breast ovarian cancer syndrome	Likely pathogenic (1)	criteria provided, single submitter	Feb 18, 2022	RCV001378528.15
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Jul 20, 2022	RCV002433536.9

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.
Pathogenic (Aug 10, 2015)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015)) Method: curation	Breast-ovarian cancer, familial 1 Affected status: unknown Allele origin: germline	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Accession: SCV000244295.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015	Publications: PubMed (1) PubMed: 21990134 Other databases http://hci-exlovd.hci.utah.edu/v… http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA1&action=search_all&search_Variant%2FDNA=c.110C%3EA Comment: IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on … (more) IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 1 (less)
Pathogenic (Oct 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial cancer of breast Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000894127.1 First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019	Publications: PubMed (1) PubMed: 25741868 pmc: 4544753 pmc: 4544753 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30
Pathogenic (Apr 19, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004215155.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Likely pathogenic (Feb 18, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001576113.4 First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024	Publications: PubMed (6) PubMed: 25823446‚ 27272900‚ 30209399‚ 19543972‚ 28664506‚ 30564348 Comment: In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more) In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25823446, 27272900, 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. This missense change has been observed in individual(s) with breast cancer (PMID: 19543972, 25823446, 28664506, 30564348). ClinVar contains an entry for this variant (Variation ID: 54131). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 37 of the BRCA1 protein (p.Thr37Lys). This variant is not present in population databases (gnomAD no frequency). (less)
Pathogenic (Jul 20, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002744812.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 28664506‚ 30209399‚ 30564348 Comment: The p.T37K pathogenic mutation (also known as c.110C>A), located in coding exon 2 of the BRCA1 gene, results from a C to A substitution at … (more) The p.T37K pathogenic mutation (also known as c.110C>A), located in coding exon 2 of the BRCA1 gene, results from a C to A substitution at nucleotide position 110. The threonine at codon 37 is replaced by lysine, an amino acid with similar properties. This alteration was identified in a Malaysian woman diagnosed with triple-negative breast cancer at age 31, as well as an African America woman diagnosed with bilateral breast cancer, at ages 27 and 33 (Yang XR et al. Breast Cancer Res Treat. 2017 Oct;165:687-697; Skendelas JP et al. Clin Case Rep. 2018 Dec;6:2457-2462). One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature. 2018 10;562:217-222). Another alteration at the same codon, p.T37R (c.110C>G), has also been determined to be functionally and structurally deleterious (Findlay GM et al. Nature. 2018 10;562:217-222; Morris JR et al. Hum Mol Genet. 2006; 15:599-606; Ransburgh DJ et al. Cancer Res. 2010; 70:988-95; Towler WI et al. Hum Mutat. 2013; Ruffner H et al. Proc. Natl. Acad. Sci. U.S.A. 2001 Apr; 98(9):5134-9; Zhu Q et al. Nature 2011 Sep; 477(7363):179-84; Brzovic PS et al. Nat. Struct. Biol. 2001 Oct;8(10):833-7; Ambry Internal Data). This variant is considered to be rare based on population 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 supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Uncertain significance (Jul 19, 2006)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 1 Affected status: yes Allele origin: germline	Breast Cancer Information Core (BIC) (BRCA1) Accession: SCV000144321.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014	Number of individuals with the variant: 1 Geographic origin: American
not provided (-)	no classification provided Method: in vitro	Breast-ovarian cancer, familial 1 Affected status: not applicable Allele origin: not applicable	Brotman Baty Institute, University of Washington Accession: SCV001242839.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020	Publications: PubMed (1) PubMed: 30209399 Other databases https://sge.gs.washington.edu/BR… https://sge.gs.washington.edu/BRCA1/ Method: saturation genome editing in haploid cells Result: LOSS_OF_FUNCTION:-2.49352324025865

Comment:

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25823446, 27272900, 30209399). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function. This missense change has been observed in individual(s) with breast cancer (PMID: 19543972, 25823446, 28664506, 30564348). ClinVar contains an entry for this variant (Variation ID: 54131). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 37 of the BRCA1 protein (p.Thr37Lys). This variant is not present in population databases (gnomAD no frequency).

Comment:

The p.T37K pathogenic mutation (also known as c.110C>A), located in coding exon 2 of the BRCA1 gene, results from a C to A substitution at nucleotide position 110. The threonine at codon 37 is replaced by lysine, an amino acid with similar properties. This alteration was identified in a Malaysian woman diagnosed with triple-negative breast cancer at age 31, as well as an African America woman diagnosed with bilateral breast cancer, at ages 27 and 33 (Yang XR et al. Breast Cancer Res Treat. 2017 Oct;165:687-697; Skendelas JP et al. Clin Case Rep. 2018 Dec;6:2457-2462). One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature. 2018 10;562:217-222). Another alteration at the same codon, p.T37R (c.110C>G), has also been determined to be functionally and structurally deleterious (Findlay GM et al. Nature. 2018 10;562:217-222; Morris JR et al. Hum Mol Genet. 2006; 15:599-606; Ransburgh DJ et al. Cancer Res. 2010; 70:988-95; Towler WI et al. Hum Mutat. 2013; Ruffner H et al. Proc. Natl. Acad. Sci. U.S.A. 2001 Apr; 98(9):5134-9; Zhu Q et al. Nature 2011 Sep; 477(7363):179-84; Brzovic PS et al. Nat. Struct. Biol. 2001 Oct;8(10):833-7; Ambry Internal Data). This variant is considered to be rare based on population 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 supporting evidence, this alteration is interpreted as a disease-causing mutation.

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.
functionally_abnormal (SO:0002218)	saturation genome editing in haploid cells Method citation(s): PubMed(1)	LOSS_OF_FUNCTION:-2.49352324025865	Brotman Baty Institute, University of Washington Accession: SCV001242839.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.110C>A, 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.110C>A, 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: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Unusual recurrence of breast cancer in a BRCA-variant patient after fat grafting.	Skendelas JP	Clinical case reports	2018	PMID: 30564348
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia.	Yang XR	Breast cancer research and treatment	2017	PMID: 28664506
Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.	Thouvenot P	PLoS genetics	2016	PMID: 27272900
Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.	Starita LM	Genetics	2015	PMID: 25823446
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).	Lindor NM	Human mutation	2012	PMID: 21990134
Characterization of BRCA1 ring finger variants of uncertain significance.	Sweet K	Breast cancer research and treatment	2010	PMID: 19543972
http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA1&action=search_all&search_Variant%2FDNA=c.110C%3EA	-	-	-	-
https://sge.gs.washington.edu/BRCA1/	-	-	-	-

Text-mined citations for rs80356880 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.110C>A (p.Thr37Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80356880 ...