TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24549	73870;73871;73872	chr2:178572487;178572486;178572485	chr2:179437214;179437213;179437212
N2AB	22908	68947;68948;68949	chr2:178572487;178572486;178572485	chr2:179437214;179437213;179437212
N2A	21981	66166;66167;66168	chr2:178572487;178572486;178572485	chr2:179437214;179437213;179437212
N2B	15484	46675;46676;46677	chr2:178572487;178572486;178572485	chr2:179437214;179437213;179437212
Novex-1	15609	47050;47051;47052	chr2:178572487;178572486;178572485	chr2:179437214;179437213;179437212
Novex-2	15676	47251;47252;47253	chr2:178572487;178572486;178572485	chr2:179437214;179437213;179437212
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-66
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1214
• Predicted PPI site: I

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
S/T	None	None	0.991	N	0.632	0.244	0.289474373501	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	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
S/A	0.0853	likely_benign	0.0807	benign	-0.791	Destabilizing	0.965	D	0.62	neutral	N	0.464263102	None	None	I
S/C	0.0963	likely_benign	0.0886	benign	-0.52	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
S/D	0.897	likely_pathogenic	0.8356	pathogenic	-0.569	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	I
S/E	0.9183	likely_pathogenic	0.8743	pathogenic	-0.553	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
S/F	0.5817	likely_pathogenic	0.4454	ambiguous	-0.903	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
S/G	0.2044	likely_benign	0.1661	benign	-1.062	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
S/H	0.7901	likely_pathogenic	0.6823	pathogenic	-1.516	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
S/I	0.5963	likely_pathogenic	0.4489	ambiguous	-0.171	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
S/K	0.9761	likely_pathogenic	0.9511	pathogenic	-0.78	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
S/L	0.2268	likely_benign	0.1802	benign	-0.171	Destabilizing	1.0	D	0.807	deleterious	N	0.486425301	None	None	I
S/M	0.3759	ambiguous	0.3158	benign	0.19	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
S/N	0.5126	ambiguous	0.4145	ambiguous	-0.812	Destabilizing	0.993	D	0.721	prob.delet.	None	None	None	None	I
S/P	0.9901	likely_pathogenic	0.9758	pathogenic	-0.344	Destabilizing	1.0	D	0.827	deleterious	D	0.524786631	None	None	I
S/Q	0.8437	likely_pathogenic	0.7757	pathogenic	-0.954	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
S/R	0.9599	likely_pathogenic	0.9198	pathogenic	-0.676	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
S/T	0.217	likely_benign	0.1784	benign	-0.785	Destabilizing	0.991	D	0.632	neutral	N	0.46887725	None	None	I
S/V	0.4227	ambiguous	0.3126	benign	-0.344	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
S/W	0.7978	likely_pathogenic	0.6461	pathogenic	-0.893	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
S/Y	0.5929	likely_pathogenic	0.4558	ambiguous	-0.629	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I

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.