TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14489	43690;43691;43692	chr2:178632541;178632540;178632539	chr2:179497268;179497267;179497266
N2AB	12848	38767;38768;38769	chr2:178632541;178632540;178632539	chr2:179497268;179497267;179497266
N2A	11921	35986;35987;35988	chr2:178632541;178632540;178632539	chr2:179497268;179497267;179497266
N2B	5424	16495;16496;16497	chr2:178632541;178632540;178632539	chr2:179497268;179497267;179497266
Novex-1	5549	16870;16871;16872	chr2:178632541;178632540;178632539	chr2:179497268;179497267;179497266
Novex-2	5616	17071;17072;17073	chr2:178632541;178632540;178632539	chr2:179497268;179497267;179497266
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-95
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.6431
• 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	D	0.603	0.488	0.563062970572	gnomAD-4.0.0	1.59278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8601E-06	0	0
K/R	None	None	0.999	D	0.549	0.551	0.541602255418	gnomAD-4.0.0	1.59277E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43509E-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	0.8473	likely_pathogenic	0.8237	pathogenic	-0.77	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
K/C	0.9361	likely_pathogenic	0.9162	pathogenic	-0.806	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/D	0.9264	likely_pathogenic	0.9117	pathogenic	-0.01	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/E	0.5958	likely_pathogenic	0.5651	pathogenic	0.121	Stabilizing	0.999	D	0.603	neutral	D	0.545803227	None	None	N
K/F	0.9377	likely_pathogenic	0.9296	pathogenic	-0.421	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/G	0.9157	likely_pathogenic	0.8994	pathogenic	-1.148	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/H	0.6208	likely_pathogenic	0.5583	ambiguous	-1.379	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/I	0.6655	likely_pathogenic	0.6376	pathogenic	0.219	Stabilizing	1.0	D	0.746	deleterious	D	0.660698043	None	None	N
K/L	0.7052	likely_pathogenic	0.6913	pathogenic	0.219	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/M	0.4892	ambiguous	0.4772	ambiguous	0.08	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/N	0.7585	likely_pathogenic	0.7336	pathogenic	-0.545	Destabilizing	1.0	D	0.707	prob.neutral	D	0.527519082	None	None	N
K/P	0.9806	likely_pathogenic	0.9733	pathogenic	-0.081	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/Q	0.3957	ambiguous	0.3569	ambiguous	-0.599	Destabilizing	1.0	D	0.69	prob.neutral	D	0.540266784	None	None	N
K/R	0.1426	likely_benign	0.1253	benign	-0.579	Destabilizing	0.999	D	0.549	neutral	D	0.660610816	None	None	N
K/S	0.8406	likely_pathogenic	0.8191	pathogenic	-1.311	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
K/T	0.4807	ambiguous	0.4548	ambiguous	-0.96	Destabilizing	1.0	D	0.749	deleterious	D	0.54909876	None	None	N
K/V	0.6819	likely_pathogenic	0.6514	pathogenic	-0.081	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/W	0.9383	likely_pathogenic	0.9226	pathogenic	-0.242	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/Y	0.8689	likely_pathogenic	0.8518	pathogenic	0.044	Stabilizing	1.0	D	0.724	prob.delet.	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.