TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14753	44482;44483;44484	chr2:178630265;178630264;178630263	chr2:179494992;179494991;179494990
N2AB	13112	39559;39560;39561	chr2:178630265;178630264;178630263	chr2:179494992;179494991;179494990
N2A	12185	36778;36779;36780	chr2:178630265;178630264;178630263	chr2:179494992;179494991;179494990
N2B	5688	17287;17288;17289	chr2:178630265;178630264;178630263	chr2:179494992;179494991;179494990
Novex-1	5813	17662;17663;17664	chr2:178630265;178630264;178630263	chr2:179494992;179494991;179494990
Novex-2	5880	17863;17864;17865	chr2:178630265;178630264;178630263	chr2:179494992;179494991;179494990
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-98
• Domain position: 79
• Structural Position: 164
• Q(SASA): 0.1285
• 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
S/Y	None	None	0.895	D	0.797	0.362	0.397540356873	gnomAD-4.0.0	1.5927E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.861E-06	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	0.1912	likely_benign	0.2411	benign	-0.691	Destabilizing	0.199	N	0.565	neutral	N	0.470914346	None	None	N
S/C	0.249	likely_benign	0.3262	benign	-0.319	Destabilizing	0.009	N	0.542	neutral	N	0.439370293	None	None	N
S/D	0.8895	likely_pathogenic	0.9529	pathogenic	0.41	Stabilizing	0.615	D	0.671	prob.neutral	None	None	None	None	N
S/E	0.9293	likely_pathogenic	0.9671	pathogenic	0.47	Stabilizing	0.615	D	0.668	prob.neutral	None	None	None	None	N
S/F	0.7456	likely_pathogenic	0.8812	pathogenic	-0.784	Destabilizing	0.895	D	0.787	deleterious	D	0.538045773	None	None	N
S/G	0.2501	likely_benign	0.3671	ambiguous	-0.99	Destabilizing	0.615	D	0.622	neutral	None	None	None	None	N
S/H	0.8382	likely_pathogenic	0.9199	pathogenic	-1.276	Destabilizing	0.992	D	0.734	deleterious	None	None	None	None	N
S/I	0.6241	likely_pathogenic	0.8072	pathogenic	0.013	Stabilizing	0.737	D	0.779	deleterious	None	None	None	None	N
S/K	0.9788	likely_pathogenic	0.9918	pathogenic	-0.105	Destabilizing	0.615	D	0.669	prob.neutral	None	None	None	None	N
S/L	0.4345	ambiguous	0.6304	pathogenic	0.013	Stabilizing	0.444	N	0.71	prob.delet.	None	None	None	None	N
S/M	0.5295	ambiguous	0.6684	pathogenic	0.052	Stabilizing	0.977	D	0.733	deleterious	None	None	None	None	N
S/N	0.553	ambiguous	0.7253	pathogenic	-0.226	Destabilizing	0.615	D	0.669	prob.neutral	None	None	None	None	N
S/P	0.9758	likely_pathogenic	0.9914	pathogenic	-0.186	Destabilizing	0.895	D	0.756	deleterious	N	0.496266922	None	None	N
S/Q	0.9085	likely_pathogenic	0.9504	pathogenic	-0.209	Destabilizing	0.919	D	0.733	deleterious	None	None	None	None	N
S/R	0.9686	likely_pathogenic	0.9879	pathogenic	-0.223	Destabilizing	0.848	D	0.763	deleterious	None	None	None	None	N
S/T	0.1167	likely_benign	0.1515	benign	-0.272	Destabilizing	0.004	N	0.343	neutral	N	0.435531082	None	None	N
S/V	0.5294	ambiguous	0.6876	pathogenic	-0.186	Destabilizing	0.444	N	0.743	deleterious	None	None	None	None	N
S/W	0.8446	likely_pathogenic	0.9365	pathogenic	-0.772	Destabilizing	0.992	D	0.831	deleterious	None	None	None	None	N
S/Y	0.6112	likely_pathogenic	0.8038	pathogenic	-0.443	Destabilizing	0.895	D	0.797	deleterious	D	0.538045773	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.