TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3103	9532;9533;9534	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648
N2AB	3103	9532;9533;9534	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648
N2A	3103	9532;9533;9534	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648
N2B	3057	9394;9395;9396	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648
Novex-1	3057	9394;9395;9396	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648
Novex-2	3057	9394;9395;9396	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648
Novex-3	3103	9532;9533;9534	chr2:178767923;178767922;178767921	chr2:179632650;179632649;179632648

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-21
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1041
• 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
I/V	rs2090782630	None	None	N	0.178	0.11	0.411001663086	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs2090782630	None	None	N	0.178	0.11	0.411001663086	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-05	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
I/A	0.6065	likely_pathogenic	0.6858	pathogenic	-2.232	Highly Destabilizing	0.055	N	0.446	neutral	None	None	None	None	N
I/C	0.6944	likely_pathogenic	0.7217	pathogenic	-1.571	Destabilizing	0.859	D	0.599	neutral	None	None	None	None	N
I/D	0.9092	likely_pathogenic	0.9452	pathogenic	-2.159	Highly Destabilizing	0.667	D	0.653	neutral	None	None	None	None	N
I/E	0.7877	likely_pathogenic	0.8646	pathogenic	-1.995	Destabilizing	0.364	N	0.637	neutral	None	None	None	None	N
I/F	0.1338	likely_benign	0.1503	benign	-1.282	Destabilizing	0.22	N	0.601	neutral	None	None	None	None	N
I/G	0.81	likely_pathogenic	0.8562	pathogenic	-2.726	Highly Destabilizing	0.22	N	0.633	neutral	None	None	None	None	N
I/H	0.6685	likely_pathogenic	0.7226	pathogenic	-2.063	Highly Destabilizing	0.958	D	0.619	neutral	None	None	None	None	N
I/K	0.6337	likely_pathogenic	0.7674	pathogenic	-1.886	Destabilizing	0.175	N	0.631	neutral	D	0.564571131	None	None	N
I/L	0.0871	likely_benign	0.1052	benign	-0.851	Destabilizing	None	N	0.19	neutral	N	0.501106713	None	None	N
I/M	0.0732	likely_benign	0.0848	benign	-0.745	Destabilizing	0.003	N	0.227	neutral	N	0.501190943	None	None	N
I/N	0.4949	ambiguous	0.5815	pathogenic	-2.046	Highly Destabilizing	0.667	D	0.648	neutral	None	None	None	None	N
I/P	0.9346	likely_pathogenic	0.9499	pathogenic	-1.286	Destabilizing	0.859	D	0.647	neutral	None	None	None	None	N
I/Q	0.6136	likely_pathogenic	0.7093	pathogenic	-1.986	Destabilizing	0.497	N	0.633	neutral	None	None	None	None	N
I/R	0.5409	ambiguous	0.6661	pathogenic	-1.479	Destabilizing	0.427	N	0.647	neutral	N	0.516666753	None	None	N
I/S	0.5624	ambiguous	0.6517	pathogenic	-2.741	Highly Destabilizing	0.124	N	0.585	neutral	None	None	None	None	N
I/T	0.5027	ambiguous	0.5676	pathogenic	-2.437	Highly Destabilizing	0.001	N	0.31	neutral	N	0.513844628	None	None	N
I/V	0.0943	likely_benign	0.0944	benign	-1.286	Destabilizing	None	N	0.178	neutral	N	0.462047758	None	None	N
I/W	0.6726	likely_pathogenic	0.7261	pathogenic	-1.59	Destabilizing	0.958	D	0.626	neutral	None	None	None	None	N
I/Y	0.3874	ambiguous	0.4582	ambiguous	-1.31	Destabilizing	0.667	D	0.613	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.