TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34992	105199;105200;105201	chr2:178531641;178531640;178531639	chr2:179396368;179396367;179396366
N2AB	33351	100276;100277;100278	chr2:178531641;178531640;178531639	chr2:179396368;179396367;179396366
N2A	32424	97495;97496;97497	chr2:178531641;178531640;178531639	chr2:179396368;179396367;179396366
N2B	25927	78004;78005;78006	chr2:178531641;178531640;178531639	chr2:179396368;179396367;179396366
Novex-1	26052	78379;78380;78381	chr2:178531641;178531640;178531639	chr2:179396368;179396367;179396366
Novex-2	26119	78580;78581;78582	chr2:178531641;178531640;178531639	chr2:179396368;179396367;179396366
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-163
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3315
• 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
N/K	None	None	1.0	N	0.731	0.296	0.360163838653	gnomAD-4.0.0	1.59091E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.4108E-04	0	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
N/A	0.5849	likely_pathogenic	0.7341	pathogenic	-0.473	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/C	0.6445	likely_pathogenic	0.7393	pathogenic	0.306	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
N/D	0.3327	likely_benign	0.5442	ambiguous	0.205	Stabilizing	0.999	D	0.768	deleterious	N	0.425969364	None	None	I
N/E	0.7684	likely_pathogenic	0.9064	pathogenic	0.17	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
N/F	0.9127	likely_pathogenic	0.9571	pathogenic	-0.889	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
N/G	0.6461	likely_pathogenic	0.7694	pathogenic	-0.636	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
N/H	0.2967	likely_benign	0.4477	ambiguous	-0.693	Destabilizing	1.0	D	0.691	prob.neutral	N	0.488537976	None	None	I
N/I	0.6568	likely_pathogenic	0.8193	pathogenic	-0.132	Destabilizing	1.0	D	0.739	prob.delet.	N	0.508662532	None	None	I
N/K	0.7664	likely_pathogenic	0.9274	pathogenic	0.207	Stabilizing	1.0	D	0.731	prob.delet.	N	0.500715052	None	None	I
N/L	0.6472	likely_pathogenic	0.772	pathogenic	-0.132	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
N/M	0.7359	likely_pathogenic	0.8487	pathogenic	0.315	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
N/P	0.8853	likely_pathogenic	0.941	pathogenic	-0.22	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
N/Q	0.7021	likely_pathogenic	0.85	pathogenic	-0.334	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
N/R	0.7217	likely_pathogenic	0.883	pathogenic	0.252	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
N/S	0.1405	likely_benign	0.1844	benign	-0.118	Destabilizing	0.999	D	0.737	prob.delet.	N	0.461639376	None	None	I
N/T	0.3655	ambiguous	0.5468	ambiguous	-0.002	Destabilizing	0.999	D	0.737	prob.delet.	N	0.517204657	None	None	I
N/V	0.598	likely_pathogenic	0.7361	pathogenic	-0.22	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/W	0.9519	likely_pathogenic	0.9772	pathogenic	-0.833	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
N/Y	0.4843	ambiguous	0.6704	pathogenic	-0.567	Destabilizing	1.0	D	0.707	prob.neutral	N	0.49827218	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.