TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9215	27868;27869;27870	chr2:178712187;178712186;178712185	chr2:179576914;179576913;179576912
N2AB	8898	26917;26918;26919	chr2:178712187;178712186;178712185	chr2:179576914;179576913;179576912
N2A	7971	24136;24137;24138	chr2:178712187;178712186;178712185	chr2:179576914;179576913;179576912
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-78
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5334
• 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
K/N	rs768260006	None	0.642	N	0.212	0.153	0.17948927462	gnomAD-4.0.0	2.05274E-06	None	None	None	None	I	None	5.9755E-05	0	None	0	0	None	0	0	8.99523E-07	0	0
K/T	None	None	0.642	N	0.292	0.237	0.314417295294	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	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
K/A	0.1733	likely_benign	0.1793	benign	-0.045	Destabilizing	0.495	N	0.314	neutral	None	None	None	None	I
K/C	0.5411	ambiguous	0.6241	pathogenic	-0.343	Destabilizing	0.995	D	0.429	neutral	None	None	None	None	I
K/D	0.2888	likely_benign	0.2909	benign	0.108	Stabilizing	0.329	N	0.318	neutral	None	None	None	None	I
K/E	0.08	likely_benign	0.0811	benign	0.131	Stabilizing	0.001	N	0.095	neutral	N	0.380887649	None	None	I
K/F	0.5085	ambiguous	0.557	ambiguous	-0.159	Destabilizing	0.981	D	0.429	neutral	None	None	None	None	I
K/G	0.3278	likely_benign	0.3346	benign	-0.271	Destabilizing	0.704	D	0.33	neutral	None	None	None	None	I
K/H	0.193	likely_benign	0.2085	benign	-0.516	Destabilizing	0.944	D	0.395	neutral	None	None	None	None	I
K/I	0.1537	likely_benign	0.1822	benign	0.476	Stabilizing	0.944	D	0.449	neutral	None	None	None	None	I
K/L	0.1844	likely_benign	0.2011	benign	0.476	Stabilizing	0.704	D	0.333	neutral	None	None	None	None	I
K/M	0.1074	likely_benign	0.1202	benign	0.191	Stabilizing	0.927	D	0.391	neutral	N	0.477552978	None	None	I
K/N	0.1827	likely_benign	0.1882	benign	0.07	Stabilizing	0.642	D	0.212	neutral	N	0.463122243	None	None	I
K/P	0.5973	likely_pathogenic	0.5597	ambiguous	0.331	Stabilizing	0.828	D	0.397	neutral	None	None	None	None	I
K/Q	0.0876	likely_benign	0.0895	benign	-0.077	Destabilizing	0.023	N	0.131	neutral	N	0.455598838	None	None	I
K/R	0.0768	likely_benign	0.0797	benign	-0.135	Destabilizing	0.006	N	0.087	neutral	N	0.426316081	None	None	I
K/S	0.1936	likely_benign	0.1987	benign	-0.445	Destabilizing	0.495	N	0.23	neutral	None	None	None	None	I
K/T	0.0746	likely_benign	0.077	benign	-0.262	Destabilizing	0.642	D	0.292	neutral	N	0.35776286	None	None	I
K/V	0.1426	likely_benign	0.165	benign	0.331	Stabilizing	0.828	D	0.358	neutral	None	None	None	None	I
K/W	0.5862	likely_pathogenic	0.6165	pathogenic	-0.149	Destabilizing	0.995	D	0.447	neutral	None	None	None	None	I
K/Y	0.4164	ambiguous	0.4436	ambiguous	0.193	Stabilizing	0.981	D	0.403	neutral	None	None	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.