TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26020	78283;78284;78285	chr2:178568074;178568073;178568072	chr2:179432801;179432800;179432799
N2AB	24379	73360;73361;73362	chr2:178568074;178568073;178568072	chr2:179432801;179432800;179432799
N2A	23452	70579;70580;70581	chr2:178568074;178568073;178568072	chr2:179432801;179432800;179432799
N2B	16955	51088;51089;51090	chr2:178568074;178568073;178568072	chr2:179432801;179432800;179432799
Novex-1	17080	51463;51464;51465	chr2:178568074;178568073;178568072	chr2:179432801;179432800;179432799
Novex-2	17147	51664;51665;51666	chr2:178568074;178568073;178568072	chr2:179432801;179432800;179432799
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-77
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2819
• 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/N	None	None	0.999	N	0.707	0.298	0.342168650903	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/R	None	None	1.0	N	0.791	0.529	0.363944505237	gnomAD-4.0.0	1.59214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.2688	likely_benign	0.3321	benign	-0.448	Destabilizing	0.998	D	0.591	neutral	None	None	None	None	I
S/C	0.1784	likely_benign	0.2314	benign	-0.287	Destabilizing	1.0	D	0.751	deleterious	N	0.482083661	None	None	I
S/D	0.9595	likely_pathogenic	0.9649	pathogenic	-0.05	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
S/E	0.9785	likely_pathogenic	0.9803	pathogenic	-0.118	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
S/F	0.7077	likely_pathogenic	0.7992	pathogenic	-0.878	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
S/G	0.447	ambiguous	0.5227	ambiguous	-0.616	Destabilizing	0.999	D	0.58	neutral	N	0.477566394	None	None	I
S/H	0.8287	likely_pathogenic	0.8533	pathogenic	-1.179	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
S/I	0.6911	likely_pathogenic	0.7641	pathogenic	-0.128	Destabilizing	1.0	D	0.818	deleterious	N	0.51965807	None	None	I
S/K	0.9909	likely_pathogenic	0.9925	pathogenic	-0.615	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
S/L	0.3544	ambiguous	0.4479	ambiguous	-0.128	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
S/M	0.5001	ambiguous	0.5809	pathogenic	0.193	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
S/N	0.5675	likely_pathogenic	0.6182	pathogenic	-0.377	Destabilizing	0.999	D	0.707	prob.neutral	N	0.50813718	None	None	I
S/P	0.9908	likely_pathogenic	0.9942	pathogenic	-0.203	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
S/Q	0.9439	likely_pathogenic	0.9505	pathogenic	-0.622	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
S/R	0.9865	likely_pathogenic	0.9898	pathogenic	-0.429	Destabilizing	1.0	D	0.791	deleterious	N	0.480598723	None	None	I
S/T	0.2005	likely_benign	0.2532	benign	-0.445	Destabilizing	0.999	D	0.592	neutral	N	0.492083614	None	None	I
S/V	0.6121	likely_pathogenic	0.6872	pathogenic	-0.203	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
S/W	0.8656	likely_pathogenic	0.917	pathogenic	-0.866	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
S/Y	0.6794	likely_pathogenic	0.7665	pathogenic	-0.601	Destabilizing	1.0	D	0.821	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.