TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22417	67474;67475;67476	chr2:178580038;178580037;178580036	chr2:179444765;179444764;179444763
N2AB	20776	62551;62552;62553	chr2:178580038;178580037;178580036	chr2:179444765;179444764;179444763
N2A	19849	59770;59771;59772	chr2:178580038;178580037;178580036	chr2:179444765;179444764;179444763
N2B	13352	40279;40280;40281	chr2:178580038;178580037;178580036	chr2:179444765;179444764;179444763
Novex-1	13477	40654;40655;40656	chr2:178580038;178580037;178580036	chr2:179444765;179444764;179444763
Novex-2	13544	40855;40856;40857	chr2:178580038;178580037;178580036	chr2:179444765;179444764;179444763
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-50
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.9267
• 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
N/Y	rs769066160	-0.43	0.998	N	0.674	0.411	0.507687591559	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/Y	rs769066160	-0.43	0.998	N	0.674	0.411	0.507687591559	gnomAD-4.0.0	1.59219E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-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
N/A	0.2009	likely_benign	0.1723	benign	-0.161	Destabilizing	0.968	D	0.601	neutral	None	None	None	None	N
N/C	0.2971	likely_benign	0.2464	benign	0.224	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/D	0.1067	likely_benign	0.0951	benign	0.092	Stabilizing	0.067	N	0.261	neutral	N	0.422565621	None	None	N
N/E	0.3538	ambiguous	0.2888	benign	0.032	Stabilizing	0.938	D	0.564	neutral	None	None	None	None	N
N/F	0.5446	ambiguous	0.4803	ambiguous	-0.717	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
N/G	0.1805	likely_benign	0.1556	benign	-0.269	Destabilizing	0.968	D	0.505	neutral	None	None	None	None	N
N/H	0.1282	likely_benign	0.109	benign	-0.267	Destabilizing	0.998	D	0.691	prob.neutral	N	0.48139519	None	None	N
N/I	0.36	ambiguous	0.2959	benign	0.026	Stabilizing	0.994	D	0.705	prob.neutral	N	0.509160684	None	None	N
N/K	0.3301	likely_benign	0.2618	benign	0.132	Stabilizing	0.958	D	0.645	neutral	N	0.474285307	None	None	N
N/L	0.2792	likely_benign	0.2439	benign	0.026	Stabilizing	0.995	D	0.683	prob.neutral	None	None	None	None	N
N/M	0.4042	ambiguous	0.3478	ambiguous	0.165	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
N/P	0.5654	likely_pathogenic	0.4681	ambiguous	-0.012	Destabilizing	0.995	D	0.648	neutral	None	None	None	None	N
N/Q	0.3402	ambiguous	0.2747	benign	-0.258	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
N/R	0.393	ambiguous	0.3163	benign	0.222	Stabilizing	0.995	D	0.697	prob.neutral	None	None	None	None	N
N/S	0.0824	likely_benign	0.0776	benign	-0.025	Destabilizing	0.958	D	0.515	neutral	N	0.503741423	None	None	N
N/T	0.162	likely_benign	0.1398	benign	0.035	Stabilizing	0.958	D	0.641	neutral	N	0.483459105	None	None	N
N/V	0.3002	likely_benign	0.2481	benign	-0.012	Destabilizing	0.995	D	0.674	neutral	None	None	None	None	N
N/W	0.7969	likely_pathogenic	0.7263	pathogenic	-0.814	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/Y	0.1974	likely_benign	0.1693	benign	-0.502	Destabilizing	0.998	D	0.674	neutral	N	0.502323829	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.