TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2139	6640;6641;6642	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174
N2AB	2139	6640;6641;6642	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174
N2A	2139	6640;6641;6642	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174
N2B	2093	6502;6503;6504	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174
Novex-1	2093	6502;6503;6504	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174
Novex-2	2093	6502;6503;6504	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174
Novex-3	2139	6640;6641;6642	chr2:178775449;178775448;178775447	chr2:179640176;179640175;179640174

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-10
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.4151
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/T	rs1250660325	None	1.0	N	0.685	0.512	0.507331908393	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
R/T	rs1250660325	None	1.0	N	0.685	0.512	0.507331908393	gnomAD-4.0.0	6.57333E-06	None	None	None	None	N	None	0	6.5505E-05	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.7702	likely_pathogenic	0.8004	pathogenic	-0.993	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
R/C	0.4656	ambiguous	0.4805	ambiguous	-0.864	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
R/D	0.9165	likely_pathogenic	0.9297	pathogenic	-0.27	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
R/E	0.6713	likely_pathogenic	0.6892	pathogenic	-0.08	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
R/F	0.9233	likely_pathogenic	0.9235	pathogenic	-0.384	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
R/G	0.6091	likely_pathogenic	0.6467	pathogenic	-1.377	Destabilizing	1.0	D	0.657	neutral	D	0.542749408	None	None	N
R/H	0.1971	likely_benign	0.2039	benign	-1.584	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
R/I	0.7908	likely_pathogenic	0.791	pathogenic	0.076	Stabilizing	1.0	D	0.721	prob.delet.	N	0.50787821	None	None	N
R/K	0.1633	likely_benign	0.1598	benign	-0.874	Destabilizing	0.997	D	0.503	neutral	N	0.481527145	None	None	N
R/L	0.6466	likely_pathogenic	0.6619	pathogenic	0.076	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
R/M	0.7435	likely_pathogenic	0.7366	pathogenic	-0.386	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
R/N	0.8483	likely_pathogenic	0.8581	pathogenic	-0.615	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
R/P	0.9258	likely_pathogenic	0.9348	pathogenic	-0.261	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
R/Q	0.1805	likely_benign	0.1832	benign	-0.56	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
R/S	0.7861	likely_pathogenic	0.8112	pathogenic	-1.356	Destabilizing	1.0	D	0.697	prob.neutral	N	0.495595166	None	None	N
R/T	0.5983	likely_pathogenic	0.6214	pathogenic	-0.951	Destabilizing	1.0	D	0.685	prob.neutral	N	0.500555274	None	None	N
R/V	0.8014	likely_pathogenic	0.8103	pathogenic	-0.261	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/W	0.5268	ambiguous	0.5216	ambiguous	0.013	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
R/Y	0.807	likely_pathogenic	0.8107	pathogenic	0.238	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.