TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35472	106639;106640;106641	chr2:178530077;178530076;178530075	chr2:179394804;179394803;179394802
N2AB	33831	101716;101717;101718	chr2:178530077;178530076;178530075	chr2:179394804;179394803;179394802
N2A	32904	98935;98936;98937	chr2:178530077;178530076;178530075	chr2:179394804;179394803;179394802
N2B	26407	79444;79445;79446	chr2:178530077;178530076;178530075	chr2:179394804;179394803;179394802
Novex-1	26532	79819;79820;79821	chr2:178530077;178530076;178530075	chr2:179394804;179394803;179394802
Novex-2	26599	80020;80021;80022	chr2:178530077;178530076;178530075	chr2:179394804;179394803;179394802
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-166
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.3073
• 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
K/N	rs776781963	-0.043	0.001	N	0.117	0.111	0.0762999501168	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	5.64E-05	None	0	None	0	0	0
K/N	rs776781963	-0.043	0.001	N	0.117	0.111	0.0762999501168	gnomAD-4.0.0	6.85476E-07	None	None	None	None	N	None	0	0	None	0	2.52576E-05	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	0.2187	likely_benign	0.2001	benign	-0.032	Destabilizing	0.055	N	0.3	neutral	None	None	None	None	N
K/C	0.7346	likely_pathogenic	0.7176	pathogenic	-0.482	Destabilizing	0.958	D	0.256	neutral	None	None	None	None	N
K/D	0.2937	likely_benign	0.2735	benign	-0.263	Destabilizing	0.055	N	0.313	neutral	None	None	None	None	N
K/E	0.1089	likely_benign	0.1017	benign	-0.284	Destabilizing	None	N	0.145	neutral	N	0.415321857	None	None	N
K/F	0.6861	likely_pathogenic	0.6534	pathogenic	-0.402	Destabilizing	0.665	D	0.291	neutral	None	None	None	None	N
K/G	0.2581	likely_benign	0.244	benign	-0.144	Destabilizing	0.103	N	0.28	neutral	None	None	None	None	N
K/H	0.3137	likely_benign	0.2898	benign	-0.24	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
K/I	0.3071	likely_benign	0.2746	benign	0.177	Stabilizing	0.665	D	0.317	neutral	None	None	None	None	N
K/L	0.3272	likely_benign	0.2972	benign	0.177	Stabilizing	0.218	N	0.317	neutral	None	None	None	None	N
K/M	0.2153	likely_benign	0.1941	benign	-0.087	Destabilizing	0.82	D	0.298	neutral	N	0.495420223	None	None	N
K/N	0.1997	likely_benign	0.1849	benign	-0.015	Destabilizing	0.001	N	0.117	neutral	N	0.377688975	None	None	N
K/P	0.5381	ambiguous	0.5182	ambiguous	0.13	Stabilizing	0.362	N	0.352	neutral	None	None	None	None	N
K/Q	0.1325	likely_benign	0.1242	benign	-0.175	Destabilizing	0.095	N	0.23	neutral	N	0.407185163	None	None	N
K/R	0.0979	likely_benign	0.0942	benign	-0.118	Destabilizing	0.08	N	0.259	neutral	N	0.457208551	None	None	N
K/S	0.2271	likely_benign	0.2141	benign	-0.402	Destabilizing	0.055	N	0.271	neutral	None	None	None	None	N
K/T	0.1313	likely_benign	0.1192	benign	-0.311	Destabilizing	0.174	N	0.287	neutral	N	0.43394769	None	None	N
K/V	0.309	likely_benign	0.2808	benign	0.13	Stabilizing	0.218	N	0.327	neutral	None	None	None	None	N
K/W	0.7657	likely_pathogenic	0.748	pathogenic	-0.489	Destabilizing	0.958	D	0.261	neutral	None	None	None	None	N
K/Y	0.5581	ambiguous	0.527	ambiguous	-0.139	Destabilizing	0.218	N	0.353	neutral	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.