TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8033	24322;24323;24324	chr2:178719293;178719292;178719291	chr2:179584020;179584019;179584018
N2AB	7716	23371;23372;23373	chr2:178719293;178719292;178719291	chr2:179584020;179584019;179584018
N2A	6789	20590;20591;20592	chr2:178719293;178719292;178719291	chr2:179584020;179584019;179584018
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-65
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.4672
• 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/Y	None	None	0.213	N	0.589	0.271	0.513112959101	gnomAD-4.0.0	1.59121E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.0691	likely_benign	0.0727	benign	-1.046	Destabilizing	0.047	N	0.259	neutral	N	0.426756011	None	None	I
S/C	0.1037	likely_benign	0.0994	benign	-0.622	Destabilizing	0.004	N	0.307	neutral	N	0.465583758	None	None	I
S/D	0.3072	likely_benign	0.3426	ambiguous	0.012	Stabilizing	0.593	D	0.34	neutral	None	None	None	None	I
S/E	0.3427	ambiguous	0.394	ambiguous	-0.008	Destabilizing	0.418	N	0.341	neutral	None	None	None	None	I
S/F	0.1354	likely_benign	0.141	benign	-1.451	Destabilizing	0.001	N	0.339	neutral	N	0.39406759	None	None	I
S/G	0.0951	likely_benign	0.0949	benign	-1.246	Destabilizing	0.228	N	0.341	neutral	None	None	None	None	I
S/H	0.1984	likely_benign	0.2239	benign	-1.736	Destabilizing	0.94	D	0.523	neutral	None	None	None	None	I
S/I	0.1073	likely_benign	0.1086	benign	-0.614	Destabilizing	0.001	N	0.319	neutral	None	None	None	None	I
S/K	0.3738	ambiguous	0.4218	ambiguous	-0.596	Destabilizing	0.418	N	0.344	neutral	None	None	None	None	I
S/L	0.0802	likely_benign	0.0838	benign	-0.614	Destabilizing	0.061	N	0.352	neutral	None	None	None	None	I
S/M	0.167	likely_benign	0.1735	benign	-0.207	Destabilizing	0.716	D	0.521	neutral	None	None	None	None	I
S/N	0.1162	likely_benign	0.1196	benign	-0.501	Destabilizing	0.593	D	0.429	neutral	None	None	None	None	I
S/P	0.0969	likely_benign	0.1305	benign	-0.728	Destabilizing	0.002	N	0.303	neutral	N	0.454713404	None	None	I
S/Q	0.2993	likely_benign	0.3533	ambiguous	-0.69	Destabilizing	0.836	D	0.445	neutral	None	None	None	None	I
S/R	0.2982	likely_benign	0.3358	benign	-0.505	Destabilizing	0.836	D	0.572	neutral	None	None	None	None	I
S/T	0.0752	likely_benign	0.0781	benign	-0.615	Destabilizing	0.183	N	0.339	neutral	N	0.386064182	None	None	I
S/V	0.1135	likely_benign	0.1203	benign	-0.728	Destabilizing	0.001	N	0.351	neutral	None	None	None	None	I
S/W	0.2157	likely_benign	0.2324	benign	-1.341	Destabilizing	0.983	D	0.543	neutral	None	None	None	None	I
S/Y	0.1018	likely_benign	0.1041	benign	-1.098	Destabilizing	0.213	N	0.589	neutral	N	0.441629463	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.