TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32883	98872;98873;98874	chr2:178539418;178539417;178539416	chr2:179404145;179404144;179404143
N2AB	31242	93949;93950;93951	chr2:178539418;178539417;178539416	chr2:179404145;179404144;179404143
N2A	30315	91168;91169;91170	chr2:178539418;178539417;178539416	chr2:179404145;179404144;179404143
N2B	23818	71677;71678;71679	chr2:178539418;178539417;178539416	chr2:179404145;179404144;179404143
Novex-1	23943	72052;72053;72054	chr2:178539418;178539417;178539416	chr2:179404145;179404144;179404143
Novex-2	24010	72253;72254;72255	chr2:178539418;178539417;178539416	chr2:179404145;179404144;179404143
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: Fn3-127
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.2968
• 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/T	rs776099498	-0.289	0.999	N	0.712	0.465	0.404592120364	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
K/T	rs776099498	-0.289	0.999	N	0.712	0.465	0.404592120364	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85948E-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	0.4601	ambiguous	0.401	ambiguous	-0.715	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
K/C	0.7072	likely_pathogenic	0.6977	pathogenic	-0.612	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/D	0.7672	likely_pathogenic	0.7067	pathogenic	-0.019	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
K/E	0.2716	likely_benign	0.2282	benign	0.13	Stabilizing	0.997	D	0.798	deleterious	N	0.395659526	None	None	N
K/F	0.7339	likely_pathogenic	0.7124	pathogenic	-0.262	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/G	0.6875	likely_pathogenic	0.621	pathogenic	-1.1	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/H	0.3758	ambiguous	0.3512	ambiguous	-1.223	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/I	0.2701	likely_benign	0.2578	benign	0.299	Stabilizing	0.999	D	0.825	deleterious	N	0.497904034	None	None	N
K/L	0.3469	ambiguous	0.3081	benign	0.299	Stabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/M	0.2426	likely_benign	0.2259	benign	0.018	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
K/N	0.6007	likely_pathogenic	0.5301	ambiguous	-0.513	Destabilizing	0.999	D	0.78	deleterious	N	0.459135002	None	None	N
K/P	0.7393	likely_pathogenic	0.6627	pathogenic	-0.01	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
K/Q	0.1588	likely_benign	0.1471	benign	-0.463	Destabilizing	0.999	D	0.773	deleterious	N	0.452977034	None	None	N
K/R	0.0979	likely_benign	0.0939	benign	-0.514	Destabilizing	0.997	D	0.751	deleterious	N	0.464732822	None	None	N
K/S	0.5653	likely_pathogenic	0.5051	ambiguous	-1.183	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
K/T	0.2109	likely_benign	0.1939	benign	-0.811	Destabilizing	0.999	D	0.712	prob.delet.	N	0.430524248	None	None	N
K/V	0.2757	likely_benign	0.2665	benign	-0.01	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
K/W	0.7666	likely_pathogenic	0.7552	pathogenic	-0.153	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/Y	0.6381	likely_pathogenic	0.6049	pathogenic	0.112	Stabilizing	1.0	D	0.857	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.