Table 6. [Notable MED12 Pathogenic Variants]. - GeneReviews®

Reference Sequences	DNA Nucleotide Change	Predicted Protein Change	Comment [Reference]
NM_005120.3 NP_005111.2	c.322C>T	p.Arg108Ter	De novo variant w/15% mosaicism in a female w/HS [Li et al 2021]
c.514G>C	p.Glu172Gln	De novo variant in a female w/XLOS [Murakami et al 2020] & a female w/NSID [Polla et al 2021]
c.617G>A	p.Arg206Gln	Reported in males w/NSID [Donnio et al 2017, Srivastava et al 2019]
c.887G>A	p.Arg296Gln	Reported in persons w/XLOS [Patil et al 2017] & NSID [Amodeo et al 2020]
NM_005120.3	c.1249-1G>C	--	De novo variant in 3 females w/NSID; leads to exon 9 skipping [Wang et al 2020, Polla et al 2021]
NM_005120.3 NP_005111.2	c.1547G>A	p.Arg516His	De novo variant in a female w/NSID [Riccardi et al 2021]
c.1862G>A	p.Arg621Gln	Reported in male sibs w/NSID [Prescott et al 2016]
c.2207_2210del	p.Thr736IlefsTer43	De novo variant in a female w/HS [Li et al 2021]
c.2312T>C	p.Ile771Thr	Reported in male sibs & their niece w/NSID [Prontera et al 2016]
c.2444G>A	p.Arg815Gln	Reported in male sibs w/NSID [Charzewska et al 2018]
c.2661_2662insG	p.Leu889ProfsTer11	De novo variant in a female w/HS [Li et al 2021]
c.2669T>A	p.Ile890Asn	De novo variant in a female w/NSID [Riccardi et al 2021]
c.2692A>G	p.Asn898Asp	Reported in a male w/FGS1 [Srivastava et al 2019] & a male w/NSID [Donnio et al 2017]
c.2735C>T	p.Ser912Leu	De novo variant in a female w/NSID [Polla et al 2021]
c.2786T>A	p.Val929Asp	De novo variant in a female w/NSID [Polla et al 2021]
c.2861T>G	p.Val954Gly	Reported in male sibs w/NSID [Charzewska et al 2018]
c.2873G>A	p.Gly958Glu	Reported in a family w/FGS1 [Rump et al 2011]
c.2881C>T	p.Arg961Trp	Most common pathogenic variant in persons w/FGS1 [Risheg et al 2007, Clark et al 2009]
c.3020A>G	p.Asn1007Ser	Recurrent variant in persons w/LS [Schwartz et al 2007, Khan et al 2016]
c.3067A>G	p.Ile1023Val	Reported in a male w/NSID [Yamamoto & Shimojima 2015]
c.3271G>A	p.Glu1091Lys	Reported in male cousins w/NSID [Charzewska et al 2018]
c.3412C>T	p.Arg1138Trp	De novo variant in 4 females w/NSID [Polla et al 2021, Riccardi et al 2021, Gonzalez et al 2021]
c.3443G>A	p.Arg1148His	Reported in males w/XLOS [Vulto-van Silfhout et al 2013, Isidor et al 2014] & females w/NSID [Charzewska et al 2018]
c.3493T>C	p.Ser1165Pro	Reported in a male w/XLOS [Vulto-van Silfhout et al 2013]
c.3640C>T	p.Arg1214Cys	Reported in male sibs w/features of FGS1 & LS [Srivastava et al 2019]
c.3646G>A	p.Val1216Met	De novo variant in a female w/NSID [Polla et al 2021]
c.3653G>A	p.Gly1218Glu	De novo variant in a female w/NSID [Polla et al 2021]
c.3883C>T	p.Arg1295Cys	Reported in a family w/NSID [Rubinato et al 2020]
c.3884G>A	p.Arg1295His	Reported in persons w/NSID [Charzewska et al 2018] & features of LS [Donnio et al 2017] & in male sibs w/features of FGS1 & LS [Srivastava et al 2019]
c.3932T>A	p.Val1311Glu	De novo variant in a female w/NSID [Polla et al 2021]
c.3935T>C	p.Leu1312Ser	De novo variant in a female w/NSID [Riccardi et al 2021]
c.4070G>A	p.Arg1357His	De novo variant in a female w/NSID [Polla et al 2021]
c.4111C>T	p.Pro1371Ser	Reported in a male w/NSID [Charzewska et al 2018]
c.4147G>A	p.Ala1383Thr	Reported in male sibs w/NSID [Langley et al 2015]
c.4400G>A	p.Arg1467Gln	De novo variant in a female w/NSID [Polla et al 2021]
c.4669T>C	p.Trp1557Arg	De novo variant in a female w/LS [Gonzalez et al 2021]
c.4832G>A	p.Arg1611His	Reported in a male w/NSID [Narayanan & Phadke 2017]
c.4903_4906delinsCCAGCA	p.Val1635ProfsTer61	Presumed de novo variant in a female w/HS [Li et al 2021]
c.5111G>A	p.Trp1704Ter	De novo variant in a female w/HS [Li et al 2021]
c.5185C>A	p.His1729Asn	Reported in a male w/XLOS [Vulto-van Silfhout et al 2013]
c.5622C>A	p.Tyr1874Ter	De novo variant in a female w/HS [Li et al 2021]
c.5898dupC	p.Ser1967GlnfsTer84	Reported in males & females w/NSID [Lesca et al 2013]
c.5919C>A	p.Tyr1973Ter	De novo variant in a female w/NSID [Polla et al 2021]
c.5922G>T	p.Gln1974His	Reported in male sibs w/NSID [Bouazzi et al 2015]
c.6169C>T	p.Gln2057Ter	De novo variant in a female w/HS [Li et al 2021]
c.6231C>A	p.Tyr2077Ter	De novo variant in a female w/NSID [Polla et al 2021]
c.6250_6258delCAGCAGCAG	p.Gln2084_Gln2086del	Reported in male sibs w/NSID & their unaffected mother [Lahbib et al 2019]
c.6268C>T	p.Gln2090Ter	De novo variant in a female w/NSID [Polla et al 2021]
c.6280C>T	p.Gln2094Ter	De novo variant in a female w/NSID [Polla et al 2021]
c.6448C>T	p.Gln2150Ter	De novo variant in a female w/NSID [Polla et al 2021]
c.6476A>C	p.Gln2159Pro	Reported in 3 male sibs w/XLOS [Rubin et al 2020]

Reference
Sequences

DNA Nucleotide
Change

Predicted Protein Change

Comment [Reference]

NM_005120.3
NP_005111.2

c.322C>T

p.Arg108Ter

De novo variant w/15% mosaicism in a female w/HS [Li et al 2021]

c.514G>C

p.Glu172Gln

De novo variant in a female w/XLOS [Murakami et al 2020] & a female w/NSID [Polla et al 2021]

c.617G>A

p.Arg206Gln

Reported in males w/NSID [Donnio et al 2017, Srivastava et al 2019]

c.887G>A

p.Arg296Gln

Reported in persons w/XLOS [Patil et al 2017] & NSID [Amodeo et al 2020]

NM_005120.3

c.1249-1G>C

De novo variant in 3 females w/NSID; leads to exon 9 skipping [Wang et al 2020, Polla et al 2021]

NM_005120.3
NP_005111.2

c.1547G>A

p.Arg516His

De novo variant in a female w/NSID [Riccardi et al 2021]

c.1862G>A

p.Arg621Gln

Reported in male sibs w/NSID [Prescott et al 2016]

c.2207_2210del

p.Thr736IlefsTer43

De novo variant in a female w/HS [Li et al 2021]

c.2312T>C

p.Ile771Thr

Reported in male sibs & their niece w/NSID [Prontera et al 2016]

c.2444G>A

p.Arg815Gln

Reported in male sibs w/NSID [Charzewska et al 2018]

c.2661_2662insG

p.Leu889ProfsTer11

De novo variant in a female w/HS [Li et al 2021]

c.2669T>A

p.Ile890Asn

De novo variant in a female w/NSID [Riccardi et al 2021]

c.2692A>G

p.Asn898Asp

Reported in a male w/FGS1 [Srivastava et al 2019] & a male w/NSID [Donnio et al 2017]

c.2735C>T

p.Ser912Leu

De novo variant in a female w/NSID [Polla et al 2021]

c.2786T>A

p.Val929Asp

De novo variant in a female w/NSID [Polla et al 2021]

c.2861T>G

p.Val954Gly

Reported in male sibs w/NSID [Charzewska et al 2018]

c.2873G>A

p.Gly958Glu

Reported in a family w/FGS1 [Rump et al 2011]

c.2881C>T

p.Arg961Trp

Most common pathogenic variant in persons w/FGS1 [Risheg et al 2007, Clark et al 2009]

c.3020A>G

p.Asn1007Ser

Recurrent variant in persons w/LS [Schwartz et al 2007, Khan et al 2016]

c.3067A>G

p.Ile1023Val

Reported in a male w/NSID [Yamamoto & Shimojima 2015]

c.3271G>A

p.Glu1091Lys

Reported in male cousins w/NSID [Charzewska et al 2018]

c.3412C>T

p.Arg1138Trp

De novo variant in 4 females w/NSID [Polla et al 2021, Riccardi et al 2021, Gonzalez et al 2021]

c.3443G>A

p.Arg1148His

Reported in males w/XLOS [Vulto-van Silfhout et al 2013, Isidor et al 2014] & females w/NSID [Charzewska et al 2018]

c.3493T>C

p.Ser1165Pro

Reported in a male w/XLOS [Vulto-van Silfhout et al 2013]

c.3640C>T

p.Arg1214Cys

Reported in male sibs w/features of FGS1 & LS [Srivastava et al 2019]

c.3646G>A

p.Val1216Met

De novo variant in a female w/NSID [Polla et al 2021]

c.3653G>A

p.Gly1218Glu

De novo variant in a female w/NSID [Polla et al 2021]

c.3883C>T

p.Arg1295Cys

Reported in a family w/NSID [Rubinato et al 2020]

c.3884G>A

p.Arg1295His

Reported in persons w/NSID [Charzewska et al 2018] & features of LS [Donnio et al 2017] & in male sibs w/features of FGS1 & LS [Srivastava et al 2019]

c.3932T>A

p.Val1311Glu

De novo variant in a female w/NSID [Polla et al 2021]

c.3935T>C

p.Leu1312Ser

De novo variant in a female w/NSID [Riccardi et al 2021]

c.4070G>A

p.Arg1357His

De novo variant in a female w/NSID [Polla et al 2021]

c.4111C>T

p.Pro1371Ser

Reported in a male w/NSID [Charzewska et al 2018]

c.4147G>A

p.Ala1383Thr

Reported in male sibs w/NSID [Langley et al 2015]

c.4400G>A

p.Arg1467Gln

De novo variant in a female w/NSID [Polla et al 2021]

c.4669T>C

p.Trp1557Arg

De novo variant in a female w/LS [Gonzalez et al 2021]

c.4832G>A

p.Arg1611His

Reported in a male w/NSID [Narayanan & Phadke 2017]

c.4903_4906delinsCCAGCA

p.Val1635ProfsTer61

Presumed de novo variant in a female w/HS [Li et al 2021]

c.5111G>A

p.Trp1704Ter

De novo variant in a female w/HS [Li et al 2021]

c.5185C>A

p.His1729Asn

Reported in a male w/XLOS [Vulto-van Silfhout et al 2013]

c.5622C>A

p.Tyr1874Ter

De novo variant in a female w/HS [Li et al 2021]

c.5898dupC

p.Ser1967GlnfsTer84

Reported in males & females w/NSID [Lesca et al 2013]

c.5919C>A

p.Tyr1973Ter

De novo variant in a female w/NSID [Polla et al 2021]

c.5922G>T

p.Gln1974His

Reported in male sibs w/NSID [Bouazzi et al 2015]

c.6169C>T

p.Gln2057Ter

De novo variant in a female w/HS [Li et al 2021]

c.6231C>A

p.Tyr2077Ter

De novo variant in a female w/NSID [Polla et al 2021]

c.6250_6258delCAGCAGCAG

p.Gln2084_Gln2086del

Reported in male sibs w/NSID & their unaffected mother [Lahbib et al 2019]

c.6268C>T

p.Gln2090Ter

De novo variant in a female w/NSID [Polla et al 2021]

c.6280C>T

p.Gln2094Ter

De novo variant in a female w/NSID [Polla et al 2021]

c.6448C>T

p.Gln2150Ter

De novo variant in a female w/NSID [Polla et al 2021]

c.6476A>C

p.Gln2159Pro

Reported in 3 male sibs w/XLOS [Rubin et al 2020]

From: MED12-Related Disorders

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.