TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13694	41305;41306;41307	chr2:178636647;178636646;178636645	chr2:179501374;179501373;179501372
N2AB	12053	36382;36383;36384	chr2:178636647;178636646;178636645	chr2:179501374;179501373;179501372
N2A	11126	33601;33602;33603	chr2:178636647;178636646;178636645	chr2:179501374;179501373;179501372
N2B	4629	14110;14111;14112	chr2:178636647;178636646;178636645	chr2:179501374;179501373;179501372
Novex-1	4754	14485;14486;14487	chr2:178636647;178636646;178636645	chr2:179501374;179501373;179501372
Novex-2	4821	14686;14687;14688	chr2:178636647;178636646;178636645	chr2:179501374;179501373;179501372
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-87
• Domain position: 11
• Structural Position: 16
• Q(SASA): 0.0437
• 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/F	None	None	1.0	D	0.749	0.416	0.74495810933	gnomAD-4.0.0	1.59223E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43303E-05	0
L/S	None	None	1.0	D	0.805	0.618	0.796996417136	gnomAD-4.0.0	1.5922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
L/A	0.9301	likely_pathogenic	0.8946	pathogenic	-2.353	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
L/C	0.9615	likely_pathogenic	0.9349	pathogenic	-1.687	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.9962	pathogenic	-2.468	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/E	0.9844	likely_pathogenic	0.9712	pathogenic	-2.308	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/F	0.7751	likely_pathogenic	0.6829	pathogenic	-1.444	Destabilizing	1.0	D	0.749	deleterious	D	0.543893063	None	None	N
L/G	0.9882	likely_pathogenic	0.9844	pathogenic	-2.836	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/H	0.9568	likely_pathogenic	0.9231	pathogenic	-2.216	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/I	0.3373	likely_benign	0.2403	benign	-0.997	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
L/K	0.9422	likely_pathogenic	0.9187	pathogenic	-1.895	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/M	0.4772	ambiguous	0.3818	ambiguous	-0.915	Destabilizing	1.0	D	0.742	deleterious	D	0.540569798	None	None	N
L/N	0.9874	likely_pathogenic	0.9773	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/P	0.9938	likely_pathogenic	0.985	pathogenic	-1.426	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/Q	0.9213	likely_pathogenic	0.8601	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/R	0.917	likely_pathogenic	0.8764	pathogenic	-1.458	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/S	0.9849	likely_pathogenic	0.9677	pathogenic	-2.739	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.540241411	None	None	N
L/T	0.9417	likely_pathogenic	0.9082	pathogenic	-2.448	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
L/V	0.4361	ambiguous	0.3058	benign	-1.426	Destabilizing	0.999	D	0.607	neutral	N	0.363677561	None	None	N
L/W	0.9598	likely_pathogenic	0.9371	pathogenic	-1.776	Destabilizing	1.0	D	0.812	deleterious	D	0.593696655	None	None	N
L/Y	0.9597	likely_pathogenic	0.9414	pathogenic	-1.494	Destabilizing	1.0	D	0.82	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.