TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16060	48403;48404;48405	chr2:178616613;178616612;178616611	chr2:179481340;179481339;179481338
N2AB	14419	43480;43481;43482	chr2:178616613;178616612;178616611	chr2:179481340;179481339;179481338
N2A	13492	40699;40700;40701	chr2:178616613;178616612;178616611	chr2:179481340;179481339;179481338
N2B	6995	21208;21209;21210	chr2:178616613;178616612;178616611	chr2:179481340;179481339;179481338
Novex-1	7120	21583;21584;21585	chr2:178616613;178616612;178616611	chr2:179481340;179481339;179481338
Novex-2	7187	21784;21785;21786	chr2:178616613;178616612;178616611	chr2:179481340;179481339;179481338
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: Fn3-4
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2884
• 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	rs2057387280	None	0.124	N	0.544	0.17	0.278143212241	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.367	ambiguous	0.4369	ambiguous	-0.411	Destabilizing	0.272	N	0.625	neutral	None	None	None	None	N
K/C	0.6109	likely_pathogenic	0.7094	pathogenic	-0.32	Destabilizing	0.968	D	0.776	deleterious	None	None	None	None	N
K/D	0.7358	likely_pathogenic	0.8054	pathogenic	-0.41	Destabilizing	0.567	D	0.68	prob.neutral	None	None	None	None	N
K/E	0.218	likely_benign	0.2534	benign	-0.29	Destabilizing	0.124	N	0.544	neutral	N	0.463013539	None	None	N
K/F	0.7952	likely_pathogenic	0.8609	pathogenic	0.097	Stabilizing	0.726	D	0.755	deleterious	None	None	None	None	N
K/G	0.4015	ambiguous	0.4662	ambiguous	-0.802	Destabilizing	0.272	N	0.694	prob.neutral	None	None	None	None	N
K/H	0.3986	ambiguous	0.4543	ambiguous	-1.271	Destabilizing	0.909	D	0.699	prob.neutral	None	None	None	None	N
K/I	0.3842	ambiguous	0.4531	ambiguous	0.618	Stabilizing	0.667	D	0.759	deleterious	N	0.482270102	None	None	N
K/L	0.3586	ambiguous	0.4275	ambiguous	0.618	Stabilizing	0.272	N	0.694	prob.neutral	None	None	None	None	N
K/M	0.2721	likely_benign	0.3118	benign	0.42	Stabilizing	0.968	D	0.685	prob.neutral	None	None	None	None	N
K/N	0.527	ambiguous	0.6025	pathogenic	-0.583	Destabilizing	0.497	N	0.599	neutral	N	0.473066289	None	None	N
K/P	0.9029	likely_pathogenic	0.9276	pathogenic	0.305	Stabilizing	0.726	D	0.703	prob.neutral	None	None	None	None	N
K/Q	0.1578	likely_benign	0.166	benign	-0.55	Destabilizing	0.009	N	0.251	neutral	N	0.449309615	None	None	N
K/R	0.0759	likely_benign	0.077	benign	-0.932	Destabilizing	0.001	N	0.197	neutral	N	0.447786301	None	None	N
K/S	0.4464	ambiguous	0.5367	ambiguous	-1.046	Destabilizing	0.272	N	0.59	neutral	None	None	None	None	N
K/T	0.2047	likely_benign	0.2475	benign	-0.732	Destabilizing	0.497	N	0.69	prob.neutral	N	0.469252181	None	None	N
K/V	0.3147	likely_benign	0.3722	ambiguous	0.305	Stabilizing	0.567	D	0.696	prob.neutral	None	None	None	None	N
K/W	0.7627	likely_pathogenic	0.8277	pathogenic	0.108	Stabilizing	0.968	D	0.741	deleterious	None	None	None	None	N
K/Y	0.7001	likely_pathogenic	0.7633	pathogenic	0.362	Stabilizing	0.726	D	0.766	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.