TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23555	70888;70889;70890	chr2:178575469;178575468;178575467	chr2:179440196;179440195;179440194
N2AB	21914	65965;65966;65967	chr2:178575469;178575468;178575467	chr2:179440196;179440195;179440194
N2A	20987	63184;63185;63186	chr2:178575469;178575468;178575467	chr2:179440196;179440195;179440194
N2B	14490	43693;43694;43695	chr2:178575469;178575468;178575467	chr2:179440196;179440195;179440194
Novex-1	14615	44068;44069;44070	chr2:178575469;178575468;178575467	chr2:179440196;179440195;179440194
Novex-2	14682	44269;44270;44271	chr2:178575469;178575468;178575467	chr2:179440196;179440195;179440194
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: Fn3-59
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5026
• 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	rs1246011660	-0.545	0.009	N	0.395	0.144	0.323886383625	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/R	rs1246011660	-0.545	0.009	N	0.395	0.144	0.323886383625	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85901E-06	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	0.8077	likely_pathogenic	0.801	pathogenic	-0.446	Destabilizing	0.904	D	0.593	neutral	None	None	None	None	N
K/C	0.9324	likely_pathogenic	0.9362	pathogenic	-0.767	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
K/D	0.9761	likely_pathogenic	0.9759	pathogenic	-0.588	Destabilizing	0.971	D	0.691	prob.neutral	None	None	None	None	N
K/E	0.792	likely_pathogenic	0.7779	pathogenic	-0.5	Destabilizing	0.681	D	0.571	neutral	N	0.490620197	None	None	N
K/F	0.9635	likely_pathogenic	0.9685	pathogenic	-0.474	Destabilizing	0.929	D	0.759	deleterious	None	None	None	None	N
K/G	0.9218	likely_pathogenic	0.9202	pathogenic	-0.686	Destabilizing	0.971	D	0.619	neutral	None	None	None	None	N
K/H	0.7477	likely_pathogenic	0.7579	pathogenic	-0.707	Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
K/I	0.8065	likely_pathogenic	0.8071	pathogenic	0.15	Stabilizing	0.002	N	0.518	neutral	None	None	None	None	N
K/L	0.739	likely_pathogenic	0.7489	pathogenic	0.15	Stabilizing	0.046	N	0.6	neutral	None	None	None	None	N
K/M	0.7177	likely_pathogenic	0.7159	pathogenic	-0.427	Destabilizing	0.918	D	0.695	prob.neutral	N	0.481523776	None	None	N
K/N	0.952	likely_pathogenic	0.9501	pathogenic	-0.512	Destabilizing	0.962	D	0.587	neutral	N	0.500677987	None	None	N
K/P	0.7433	likely_pathogenic	0.7624	pathogenic	-0.024	Destabilizing	0.995	D	0.704	prob.neutral	None	None	None	None	N
K/Q	0.4917	ambiguous	0.4738	ambiguous	-0.496	Destabilizing	0.752	D	0.599	neutral	N	0.498933036	None	None	N
K/R	0.104	likely_benign	0.102	benign	-0.263	Destabilizing	0.009	N	0.395	neutral	N	0.508917956	None	None	N
K/S	0.918	likely_pathogenic	0.9162	pathogenic	-0.882	Destabilizing	0.904	D	0.577	neutral	None	None	None	None	N
K/T	0.8019	likely_pathogenic	0.7929	pathogenic	-0.626	Destabilizing	0.882	D	0.643	neutral	N	0.513939774	None	None	N
K/V	0.7308	likely_pathogenic	0.73	pathogenic	-0.024	Destabilizing	0.059	N	0.604	neutral	None	None	None	None	N
K/W	0.9582	likely_pathogenic	0.965	pathogenic	-0.548	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
K/Y	0.9204	likely_pathogenic	0.9283	pathogenic	-0.233	Destabilizing	0.758	D	0.754	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.