TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19543	58852;58853;58854	chr2:178593673;178593672;178593671	chr2:179458400;179458399;179458398
N2AB	17902	53929;53930;53931	chr2:178593673;178593672;178593671	chr2:179458400;179458399;179458398
N2A	16975	51148;51149;51150	chr2:178593673;178593672;178593671	chr2:179458400;179458399;179458398
N2B	10478	31657;31658;31659	chr2:178593673;178593672;178593671	chr2:179458400;179458399;179458398
Novex-1	10603	32032;32033;32034	chr2:178593673;178593672;178593671	chr2:179458400;179458399;179458398
Novex-2	10670	32233;32234;32235	chr2:178593673;178593672;178593671	chr2:179458400;179458399;179458398
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: Fn3-29
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.7917
• 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/E	None	None	0.999	N	0.613	0.337	0.357313475932	gnomAD-4.0.0	1.59232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.6806	likely_pathogenic	0.6302	pathogenic	-0.034	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
K/C	0.832	likely_pathogenic	0.8126	pathogenic	-0.519	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.7679	likely_pathogenic	0.7298	pathogenic	-0.292	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
K/E	0.5704	likely_pathogenic	0.5168	ambiguous	-0.311	Destabilizing	0.999	D	0.613	neutral	N	0.502818703	None	None	N
K/F	0.9324	likely_pathogenic	0.916	pathogenic	-0.4	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/G	0.5926	likely_pathogenic	0.5514	ambiguous	-0.145	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/H	0.41	ambiguous	0.3843	ambiguous	-0.21	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/I	0.8326	likely_pathogenic	0.7901	pathogenic	0.172	Stabilizing	1.0	D	0.693	prob.neutral	N	0.485398116	None	None	N
K/L	0.7227	likely_pathogenic	0.6803	pathogenic	0.172	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/M	0.6143	likely_pathogenic	0.5706	pathogenic	-0.137	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/N	0.6353	likely_pathogenic	0.5956	pathogenic	-0.054	Destabilizing	1.0	D	0.725	prob.delet.	N	0.427203437	None	None	N
K/P	0.8743	likely_pathogenic	0.8446	pathogenic	0.126	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/Q	0.3103	likely_benign	0.2769	benign	-0.204	Destabilizing	1.0	D	0.724	prob.delet.	N	0.479357729	None	None	N
K/R	0.0948	likely_benign	0.0923	benign	-0.129	Destabilizing	0.999	D	0.611	neutral	N	0.492911141	None	None	N
K/S	0.6809	likely_pathogenic	0.6283	pathogenic	-0.429	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
K/T	0.534	ambiguous	0.48	ambiguous	-0.337	Destabilizing	1.0	D	0.697	prob.neutral	N	0.473281342	None	None	N
K/V	0.7501	likely_pathogenic	0.6953	pathogenic	0.126	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/W	0.9136	likely_pathogenic	0.8967	pathogenic	-0.496	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/Y	0.8063	likely_pathogenic	0.7739	pathogenic	-0.147	Destabilizing	1.0	D	0.667	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.