TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33943	102052;102053;102054	chr2:178534788;178534787;178534786	chr2:179399515;179399514;179399513
N2AB	32302	97129;97130;97131	chr2:178534788;178534787;178534786	chr2:179399515;179399514;179399513
N2A	31375	94348;94349;94350	chr2:178534788;178534787;178534786	chr2:179399515;179399514;179399513
N2B	24878	74857;74858;74859	chr2:178534788;178534787;178534786	chr2:179399515;179399514;179399513
Novex-1	25003	75232;75233;75234	chr2:178534788;178534787;178534786	chr2:179399515;179399514;179399513
Novex-2	25070	75433;75434;75435	chr2:178534788;178534787;178534786	chr2:179399515;179399514;179399513
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Kinase-1
• Domain position: 131
• Q(SASA): 0.1295
• 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
E/G	None	None	None	N	None	0.408	0.319114376414	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
E/A	0.4052	ambiguous	0.3633	ambiguous	0.426	Stabilizing	None	None	None	None	N	0.502060981	None	None	N
E/C	0.9475	likely_pathogenic	0.9369	pathogenic	0.268	Stabilizing	None	None	None	None	None	None	None	None	N
E/D	0.226	likely_benign	0.2122	benign	-1.621	Destabilizing	None	None	None	None	N	0.437972217	None	None	N
E/F	0.9608	likely_pathogenic	0.9363	pathogenic	1.056	Stabilizing	None	None	None	None	None	None	None	None	N
E/G	0.3563	ambiguous	0.3435	ambiguous	-0.07	Destabilizing	None	None	None	None	N	0.518203869	None	None	N
E/H	0.7936	likely_pathogenic	0.7447	pathogenic	0.655	Stabilizing	None	None	None	None	None	None	None	None	N
E/I	0.8249	likely_pathogenic	0.7864	pathogenic	1.798	Stabilizing	None	None	None	None	None	None	None	None	N
E/K	0.419	ambiguous	0.3877	ambiguous	-0.203	Destabilizing	None	None	None	None	N	0.476334945	None	None	N
E/L	0.8711	likely_pathogenic	0.842	pathogenic	1.798	Stabilizing	None	None	None	None	None	None	None	None	N
E/M	0.8845	likely_pathogenic	0.8629	pathogenic	2.21	Highly Stabilizing	None	None	None	None	None	None	None	None	N
E/N	0.5481	ambiguous	0.5209	ambiguous	-1.006	Destabilizing	None	None	None	None	None	None	None	None	N
E/P	0.8806	likely_pathogenic	0.8499	pathogenic	1.367	Stabilizing	None	None	None	None	None	None	None	None	N
E/Q	0.3301	likely_benign	0.3149	benign	-0.606	Destabilizing	None	None	None	None	N	0.500772901	None	None	N
E/R	0.5457	ambiguous	0.4932	ambiguous	-0.213	Destabilizing	None	None	None	None	None	None	None	None	N
E/S	0.4215	ambiguous	0.3702	ambiguous	-1.327	Destabilizing	None	None	None	None	None	None	None	None	N
E/T	0.6057	likely_pathogenic	0.5325	ambiguous	-0.875	Destabilizing	None	None	None	None	None	None	None	None	N
E/V	0.6641	likely_pathogenic	0.6312	pathogenic	1.367	Stabilizing	None	None	None	None	N	0.507316443	None	None	N
E/W	0.9783	likely_pathogenic	0.966	pathogenic	0.901	Stabilizing	None	None	None	None	None	None	None	None	N
E/Y	0.8961	likely_pathogenic	0.8593	pathogenic	1.265	Stabilizing	None	None	None	None	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.