TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30189	90790;90791;90792	chr2:178552335;178552334;178552333	chr2:179417062;179417061;179417060
N2AB	28548	85867;85868;85869	chr2:178552335;178552334;178552333	chr2:179417062;179417061;179417060
N2A	27621	83086;83087;83088	chr2:178552335;178552334;178552333	chr2:179417062;179417061;179417060
N2B	21124	63595;63596;63597	chr2:178552335;178552334;178552333	chr2:179417062;179417061;179417060
Novex-1	21249	63970;63971;63972	chr2:178552335;178552334;178552333	chr2:179417062;179417061;179417060
Novex-2	21316	64171;64172;64173	chr2:178552335;178552334;178552333	chr2:179417062;179417061;179417060
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-148
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.1051
• 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	0.003	N	0.393	0.313	0.463157528383	gnomAD-4.0.0	6.88953E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02485E-07	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	0.9225	likely_pathogenic	0.8775	pathogenic	-2.226	Highly Destabilizing	0.575	D	0.721	prob.delet.	None	None	None	None	N
L/C	0.8555	likely_pathogenic	0.7933	pathogenic	-1.712	Destabilizing	0.991	D	0.782	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9988	pathogenic	-2.943	Highly Destabilizing	0.967	D	0.866	deleterious	None	None	None	None	N
L/E	0.9969	likely_pathogenic	0.9935	pathogenic	-2.616	Highly Destabilizing	0.906	D	0.85	deleterious	None	None	None	None	N
L/F	0.2314	likely_benign	0.1828	benign	-1.42	Destabilizing	0.003	N	0.393	neutral	N	0.521369358	None	None	N
L/G	0.9869	likely_pathogenic	0.9769	pathogenic	-2.83	Highly Destabilizing	0.906	D	0.831	deleterious	None	None	None	None	N
L/H	0.9788	likely_pathogenic	0.9641	pathogenic	-2.802	Highly Destabilizing	0.991	D	0.855	deleterious	None	None	None	None	N
L/I	0.1747	likely_benign	0.133	benign	-0.414	Destabilizing	0.218	N	0.688	prob.neutral	None	None	None	None	N
L/K	0.9925	likely_pathogenic	0.986	pathogenic	-1.751	Destabilizing	0.906	D	0.821	deleterious	None	None	None	None	N
L/M	0.2202	likely_benign	0.1816	benign	-0.689	Destabilizing	0.879	D	0.698	prob.neutral	D	0.529611792	None	None	N
L/N	0.9958	likely_pathogenic	0.9912	pathogenic	-2.482	Highly Destabilizing	0.967	D	0.861	deleterious	None	None	None	None	N
L/P	0.997	likely_pathogenic	0.9955	pathogenic	-1.008	Destabilizing	0.967	D	0.862	deleterious	None	None	None	None	N
L/Q	0.9832	likely_pathogenic	0.9649	pathogenic	-2.051	Highly Destabilizing	0.967	D	0.829	deleterious	None	None	None	None	N
L/R	0.9838	likely_pathogenic	0.9733	pathogenic	-2.063	Highly Destabilizing	0.906	D	0.839	deleterious	None	None	None	None	N
L/S	0.9905	likely_pathogenic	0.9793	pathogenic	-3.016	Highly Destabilizing	0.879	D	0.812	deleterious	D	0.557630775	None	None	N
L/T	0.9638	likely_pathogenic	0.9345	pathogenic	-2.508	Highly Destabilizing	0.575	D	0.759	deleterious	None	None	None	None	N
L/V	0.2218	likely_benign	0.1802	benign	-1.008	Destabilizing	0.006	N	0.361	neutral	N	0.494301881	None	None	N
L/W	0.8641	likely_pathogenic	0.807	pathogenic	-1.809	Destabilizing	0.965	D	0.831	deleterious	D	0.557630775	None	None	N
L/Y	0.8553	likely_pathogenic	0.7816	pathogenic	-1.546	Destabilizing	0.704	D	0.803	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.