TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14503	43732;43733;43734	chr2:178632387;178632386;178632385	chr2:179497114;179497113;179497112
N2AB	12862	38809;38810;38811	chr2:178632387;178632386;178632385	chr2:179497114;179497113;179497112
N2A	11935	36028;36029;36030	chr2:178632387;178632386;178632385	chr2:179497114;179497113;179497112
N2B	5438	16537;16538;16539	chr2:178632387;178632386;178632385	chr2:179497114;179497113;179497112
Novex-1	5563	16912;16913;16914	chr2:178632387;178632386;178632385	chr2:179497114;179497113;179497112
Novex-2	5630	17113;17114;17115	chr2:178632387;178632386;178632385	chr2:179497114;179497113;179497112
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-96
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.159
• 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
L/P	None	None	0.997	D	0.842	0.665	0.890315468549	gnomAD-4.0.0	3.45772E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.52594E-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
L/A	0.9061	likely_pathogenic	0.889	pathogenic	-2.17	Highly Destabilizing	0.953	D	0.593	neutral	None	None	None	None	N
L/C	0.9477	likely_pathogenic	0.9458	pathogenic	-1.452	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9989	pathogenic	-2.045	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
L/E	0.9911	likely_pathogenic	0.9898	pathogenic	-1.819	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
L/F	0.802	likely_pathogenic	0.7913	pathogenic	-1.158	Destabilizing	0.982	D	0.651	neutral	D	0.682334681	None	None	N
L/G	0.989	likely_pathogenic	0.9881	pathogenic	-2.718	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
L/H	0.9886	likely_pathogenic	0.9874	pathogenic	-2.105	Highly Destabilizing	0.999	D	0.811	deleterious	D	0.680931111	None	None	N
L/I	0.2698	likely_benign	0.23	benign	-0.605	Destabilizing	0.02	N	0.213	neutral	N	0.51002097	None	None	N
L/K	0.9879	likely_pathogenic	0.9858	pathogenic	-1.593	Destabilizing	0.993	D	0.807	deleterious	None	None	None	None	N
L/M	0.4013	ambiguous	0.3886	ambiguous	-0.6	Destabilizing	0.986	D	0.688	prob.neutral	None	None	None	None	N
L/N	0.9933	likely_pathogenic	0.993	pathogenic	-1.899	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
L/P	0.8898	likely_pathogenic	0.8407	pathogenic	-1.105	Destabilizing	0.997	D	0.842	deleterious	D	0.65130003	None	None	N
L/Q	0.9669	likely_pathogenic	0.9632	pathogenic	-1.733	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
L/R	0.9782	likely_pathogenic	0.9758	pathogenic	-1.402	Destabilizing	0.997	D	0.801	deleterious	D	0.681827887	None	None	N
L/S	0.9817	likely_pathogenic	0.9827	pathogenic	-2.65	Highly Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
L/T	0.9373	likely_pathogenic	0.9362	pathogenic	-2.27	Highly Destabilizing	0.986	D	0.746	deleterious	None	None	None	None	N
L/V	0.3478	ambiguous	0.2996	benign	-1.105	Destabilizing	0.76	D	0.352	neutral	D	0.683043451	None	None	N
L/W	0.9755	likely_pathogenic	0.9767	pathogenic	-1.496	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
L/Y	0.9906	likely_pathogenic	0.99	pathogenic	-1.173	Destabilizing	0.998	D	0.792	deleterious	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.