TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16574	49945;49946;49947	chr2:178613001;178613000;178612999	chr2:179477728;179477727;179477726
N2AB	14933	45022;45023;45024	chr2:178613001;178613000;178612999	chr2:179477728;179477727;179477726
N2A	14006	42241;42242;42243	chr2:178613001;178613000;178612999	chr2:179477728;179477727;179477726
N2B	7509	22750;22751;22752	chr2:178613001;178613000;178612999	chr2:179477728;179477727;179477726
Novex-1	7634	23125;23126;23127	chr2:178613001;178613000;178612999	chr2:179477728;179477727;179477726
Novex-2	7701	23326;23327;23328	chr2:178613001;178613000;178612999	chr2:179477728;179477727;179477726
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: Fn3-8
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4834
• 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/N	None	None	1.0	N	0.718	0.286	0.134241683229	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5555	ambiguous	0.6733	pathogenic	-0.186	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
K/C	0.8717	likely_pathogenic	0.8936	pathogenic	-0.427	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
K/D	0.906	likely_pathogenic	0.9506	pathogenic	-0.049	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/E	0.5024	ambiguous	0.6826	pathogenic	0.023	Stabilizing	0.999	D	0.615	neutral	N	0.478818169	None	None	N
K/F	0.9214	likely_pathogenic	0.951	pathogenic	-0.163	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/G	0.7835	likely_pathogenic	0.8614	pathogenic	-0.459	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/H	0.5816	likely_pathogenic	0.6431	pathogenic	-0.659	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/I	0.5958	likely_pathogenic	0.7085	pathogenic	0.483	Stabilizing	1.0	D	0.807	deleterious	D	0.573724852	None	None	N
K/L	0.5562	ambiguous	0.6519	pathogenic	0.483	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/M	0.4766	ambiguous	0.6087	pathogenic	0.064	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/N	0.8314	likely_pathogenic	0.9042	pathogenic	-0.115	Destabilizing	1.0	D	0.718	prob.delet.	N	0.470145164	None	None	N
K/P	0.5773	likely_pathogenic	0.6444	pathogenic	0.289	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/Q	0.2888	likely_benign	0.3525	ambiguous	-0.148	Destabilizing	1.0	D	0.698	prob.neutral	N	0.481537964	None	None	N
K/R	0.0994	likely_benign	0.0994	benign	-0.212	Destabilizing	0.999	D	0.583	neutral	N	0.465889309	None	None	N
K/S	0.7518	likely_pathogenic	0.8405	pathogenic	-0.604	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
K/T	0.4589	ambiguous	0.6084	pathogenic	-0.347	Destabilizing	1.0	D	0.786	deleterious	N	0.475912872	None	None	N
K/V	0.5212	ambiguous	0.6166	pathogenic	0.289	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/W	0.9235	likely_pathogenic	0.9498	pathogenic	-0.178	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8596	likely_pathogenic	0.9073	pathogenic	0.154	Stabilizing	1.0	D	0.804	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.