TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7775	23548;23549;23550	chr2:178720439;178720438;178720437	chr2:179585166;179585165;179585164
N2AB	7458	22597;22598;22599	chr2:178720439;178720438;178720437	chr2:179585166;179585165;179585164
N2A	6531	19816;19817;19818	chr2:178720439;178720438;178720437	chr2:179585166;179585165;179585164
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-62
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.4742
• 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/Q	rs771592871	-0.479	0.252	N	0.615	0.217	0.190952846119	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
K/Q	rs771592871	-0.479	0.252	N	0.615	0.217	0.190952846119	gnomAD-4.0.0	1.90987E-05	None	None	None	None	N	None	0	0	None	0	3.32779E-04	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	0.8299	likely_pathogenic	0.8179	pathogenic	-0.593	Destabilizing	0.303	N	0.517	neutral	None	None	None	None	N
K/C	0.9292	likely_pathogenic	0.9279	pathogenic	-0.862	Destabilizing	0.989	D	0.621	neutral	None	None	None	None	N
K/D	0.9656	likely_pathogenic	0.9606	pathogenic	-0.585	Destabilizing	0.787	D	0.611	neutral	None	None	None	None	N
K/E	0.6138	likely_pathogenic	0.5952	pathogenic	-0.478	Destabilizing	0.107	N	0.573	neutral	N	0.496349383	None	None	N
K/F	0.9314	likely_pathogenic	0.9278	pathogenic	-0.389	Destabilizing	0.749	D	0.627	neutral	None	None	None	None	N
K/G	0.942	likely_pathogenic	0.936	pathogenic	-0.953	Destabilizing	0.513	D	0.607	neutral	None	None	None	None	N
K/H	0.5882	likely_pathogenic	0.5807	pathogenic	-1.356	Destabilizing	0.921	D	0.597	neutral	None	None	None	None	N
K/I	0.5243	ambiguous	0.5187	ambiguous	0.339	Stabilizing	0.039	N	0.631	neutral	N	0.479342489	None	None	N
K/L	0.6698	likely_pathogenic	0.6643	pathogenic	0.339	Stabilizing	0.015	N	0.585	neutral	None	None	None	None	N
K/M	0.4594	ambiguous	0.4536	ambiguous	0.251	Stabilizing	0.472	N	0.611	neutral	None	None	None	None	N
K/N	0.9032	likely_pathogenic	0.8868	pathogenic	-0.737	Destabilizing	0.736	D	0.59	neutral	N	0.520381035	None	None	N
K/P	0.9957	likely_pathogenic	0.9954	pathogenic	0.058	Stabilizing	0.882	D	0.634	neutral	None	None	None	None	N
K/Q	0.3105	likely_benign	0.3071	benign	-0.863	Destabilizing	0.252	N	0.615	neutral	N	0.500869768	None	None	N
K/R	0.1142	likely_benign	0.1101	benign	-0.733	Destabilizing	0.001	N	0.389	neutral	N	0.480726569	None	None	N
K/S	0.871	likely_pathogenic	0.8564	pathogenic	-1.352	Destabilizing	0.345	N	0.554	neutral	None	None	None	None	N
K/T	0.444	ambiguous	0.4214	ambiguous	-1.046	Destabilizing	0.003	N	0.365	neutral	N	0.468893422	None	None	N
K/V	0.5202	ambiguous	0.5056	ambiguous	0.058	Stabilizing	0.001	N	0.505	neutral	None	None	None	None	N
K/W	0.9294	likely_pathogenic	0.9265	pathogenic	-0.291	Destabilizing	0.992	D	0.642	neutral	None	None	None	None	N
K/Y	0.8695	likely_pathogenic	0.8694	pathogenic	0.057	Stabilizing	0.515	D	0.642	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.