TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17241	51946;51947;51948	chr2:178609702;178609701;178609700	chr2:179474429;179474428;179474427
N2AB	15600	47023;47024;47025	chr2:178609702;178609701;178609700	chr2:179474429;179474428;179474427
N2A	14673	44242;44243;44244	chr2:178609702;178609701;178609700	chr2:179474429;179474428;179474427
N2B	8176	24751;24752;24753	chr2:178609702;178609701;178609700	chr2:179474429;179474428;179474427
Novex-1	8301	25126;25127;25128	chr2:178609702;178609701;178609700	chr2:179474429;179474428;179474427
Novex-2	8368	25327;25328;25329	chr2:178609702;178609701;178609700	chr2:179474429;179474428;179474427
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: Fn3-13
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.566
• 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/R	None	None	0.997	N	0.758	0.236	0.335910606209	gnomAD-4.0.0	6.92065E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.07652E-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
K/A	0.5465	ambiguous	0.5533	ambiguous	-0.215	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
K/C	0.8349	likely_pathogenic	0.8298	pathogenic	-0.378	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/D	0.8967	likely_pathogenic	0.8948	pathogenic	0.167	Stabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
K/E	0.3512	ambiguous	0.3619	ambiguous	0.21	Stabilizing	0.997	D	0.826	deleterious	N	0.49205271	None	None	N
K/F	0.8609	likely_pathogenic	0.8517	pathogenic	-0.21	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/G	0.8272	likely_pathogenic	0.8153	pathogenic	-0.485	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/H	0.5668	likely_pathogenic	0.5664	pathogenic	-0.751	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
K/I	0.3216	likely_benign	0.3398	benign	0.435	Stabilizing	0.999	D	0.8	deleterious	N	0.432353832	None	None	N
K/L	0.3975	ambiguous	0.407	ambiguous	0.435	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/M	0.2553	likely_benign	0.2687	benign	0.26	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/N	0.7446	likely_pathogenic	0.7507	pathogenic	-0.013	Destabilizing	0.999	D	0.779	deleterious	N	0.480080015	None	None	N
K/P	0.7967	likely_pathogenic	0.792	pathogenic	0.249	Stabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
K/Q	0.2309	likely_benign	0.2338	benign	-0.176	Destabilizing	0.999	D	0.779	deleterious	N	0.470813433	None	None	N
K/R	0.0983	likely_benign	0.0987	benign	-0.211	Destabilizing	0.997	D	0.758	deleterious	N	0.459615004	None	None	N
K/S	0.7449	likely_pathogenic	0.736	pathogenic	-0.625	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
K/T	0.2664	likely_benign	0.2655	benign	-0.406	Destabilizing	0.999	D	0.786	deleterious	N	0.422155481	None	None	N
K/V	0.2825	likely_benign	0.2996	benign	0.249	Stabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
K/W	0.8884	likely_pathogenic	0.8786	pathogenic	-0.127	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Y	0.7984	likely_pathogenic	0.784	pathogenic	0.194	Stabilizing	1.0	D	0.805	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.