TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20197	60814;60815;60816	chr2:178591136;178591135;178591134	chr2:179455863;179455862;179455861
N2AB	18556	55891;55892;55893	chr2:178591136;178591135;178591134	chr2:179455863;179455862;179455861
N2A	17629	53110;53111;53112	chr2:178591136;178591135;178591134	chr2:179455863;179455862;179455861
N2B	11132	33619;33620;33621	chr2:178591136;178591135;178591134	chr2:179455863;179455862;179455861
Novex-1	11257	33994;33995;33996	chr2:178591136;178591135;178591134	chr2:179455863;179455862;179455861
Novex-2	11324	34195;34196;34197	chr2:178591136;178591135;178591134	chr2:179455863;179455862;179455861
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: Fn3-34
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.9021
• 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	0.993	N	0.711	0.266	0.301455362545	gnomAD-4.0.0	6.84413E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99653E-07	0	0
K/T	None	None	0.993	N	0.657	0.281	0.400899426204	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	0.218	likely_benign	0.2413	benign	0.099	Stabilizing	0.983	D	0.637	neutral	None	None	None	None	N
K/C	0.6949	likely_pathogenic	0.7037	pathogenic	-0.137	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
K/D	0.5266	ambiguous	0.5655	pathogenic	-0.095	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
K/E	0.1168	likely_benign	0.1334	benign	-0.106	Destabilizing	0.977	D	0.655	neutral	N	0.494737937	None	None	N
K/F	0.7633	likely_pathogenic	0.8005	pathogenic	-0.189	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.4126	ambiguous	0.4626	ambiguous	-0.062	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
K/H	0.3779	ambiguous	0.3992	ambiguous	-0.281	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
K/I	0.2609	likely_benign	0.2851	benign	0.439	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.2648	likely_benign	0.2927	benign	0.439	Stabilizing	0.995	D	0.589	neutral	None	None	None	None	N
K/M	0.197	likely_benign	0.2134	benign	0.177	Stabilizing	1.0	D	0.712	prob.delet.	N	0.475487069	None	None	N
K/N	0.4358	ambiguous	0.4861	ambiguous	0.32	Stabilizing	0.993	D	0.711	prob.delet.	N	0.47537171	None	None	N
K/P	0.6819	likely_pathogenic	0.7245	pathogenic	0.351	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.1274	likely_benign	0.1376	benign	0.141	Stabilizing	0.993	D	0.707	prob.neutral	D	0.522060612	None	None	N
K/R	0.0865	likely_benign	0.0919	benign	0.047	Stabilizing	0.235	N	0.281	neutral	N	0.518134872	None	None	N
K/S	0.3495	ambiguous	0.3904	ambiguous	-0.086	Destabilizing	0.983	D	0.658	neutral	None	None	None	None	N
K/T	0.1517	likely_benign	0.1662	benign	0.032	Stabilizing	0.993	D	0.657	neutral	N	0.52119382	None	None	N
K/V	0.2054	likely_benign	0.2282	benign	0.351	Stabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/W	0.7911	likely_pathogenic	0.8157	pathogenic	-0.258	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/Y	0.6777	likely_pathogenic	0.7148	pathogenic	0.104	Stabilizing	0.999	D	0.711	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.