TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16360	49303;49304;49305	chr2:178614319;178614318;178614317	chr2:179479046;179479045;179479044
N2AB	14719	44380;44381;44382	chr2:178614319;178614318;178614317	chr2:179479046;179479045;179479044
N2A	13792	41599;41600;41601	chr2:178614319;178614318;178614317	chr2:179479046;179479045;179479044
N2B	7295	22108;22109;22110	chr2:178614319;178614318;178614317	chr2:179479046;179479045;179479044
Novex-1	7420	22483;22484;22485	chr2:178614319;178614318;178614317	chr2:179479046;179479045;179479044
Novex-2	7487	22684;22685;22686	chr2:178614319;178614318;178614317	chr2:179479046;179479045;179479044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-6
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.1854
• 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
I/F	None	None	0.638	N	0.667	0.216	0.542187413537	gnomAD-4.0.0	6.84612E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16017E-05	0
I/L	None	None	0.043	N	0.442	0.101	0.44750879378	gnomAD-4.0.0	6.84612E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99823E-07	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
I/A	0.6508	likely_pathogenic	0.7362	pathogenic	-2.258	Highly Destabilizing	0.25	N	0.611	neutral	None	None	None	None	N
I/C	0.7542	likely_pathogenic	0.8144	pathogenic	-1.627	Destabilizing	0.947	D	0.74	deleterious	None	None	None	None	N
I/D	0.9813	likely_pathogenic	0.9892	pathogenic	-1.928	Destabilizing	0.826	D	0.856	deleterious	None	None	None	None	N
I/E	0.9631	likely_pathogenic	0.9759	pathogenic	-1.707	Destabilizing	0.826	D	0.843	deleterious	None	None	None	None	N
I/F	0.3366	likely_benign	0.4411	ambiguous	-1.348	Destabilizing	0.638	D	0.667	neutral	N	0.476761009	None	None	N
I/G	0.9376	likely_pathogenic	0.9628	pathogenic	-2.805	Highly Destabilizing	0.826	D	0.833	deleterious	None	None	None	None	N
I/H	0.9213	likely_pathogenic	0.9574	pathogenic	-2.159	Highly Destabilizing	0.982	D	0.829	deleterious	None	None	None	None	N
I/K	0.9152	likely_pathogenic	0.9356	pathogenic	-1.56	Destabilizing	0.826	D	0.843	deleterious	None	None	None	None	N
I/L	0.2549	likely_benign	0.2994	benign	-0.696	Destabilizing	0.043	N	0.442	neutral	N	0.480578566	None	None	N
I/M	0.2085	likely_benign	0.237	benign	-0.699	Destabilizing	0.638	D	0.645	neutral	D	0.593565552	None	None	N
I/N	0.8218	likely_pathogenic	0.8709	pathogenic	-1.83	Destabilizing	0.916	D	0.855	deleterious	D	0.564742618	None	None	N
I/P	0.9362	likely_pathogenic	0.9562	pathogenic	-1.195	Destabilizing	0.826	D	0.858	deleterious	None	None	None	None	N
I/Q	0.9206	likely_pathogenic	0.945	pathogenic	-1.67	Destabilizing	0.935	D	0.857	deleterious	None	None	None	None	N
I/R	0.8762	likely_pathogenic	0.9106	pathogenic	-1.379	Destabilizing	0.826	D	0.859	deleterious	None	None	None	None	N
I/S	0.748	likely_pathogenic	0.8154	pathogenic	-2.632	Highly Destabilizing	0.638	D	0.787	deleterious	D	0.584426469	None	None	N
I/T	0.5958	likely_pathogenic	0.6991	pathogenic	-2.244	Highly Destabilizing	0.201	N	0.755	deleterious	D	0.564096574	None	None	N
I/V	0.0721	likely_benign	0.084	benign	-1.195	Destabilizing	0.001	N	0.216	neutral	N	0.428111879	None	None	N
I/W	0.9491	likely_pathogenic	0.9729	pathogenic	-1.611	Destabilizing	0.982	D	0.78	deleterious	None	None	None	None	N
I/Y	0.8306	likely_pathogenic	0.8868	pathogenic	-1.314	Destabilizing	0.826	D	0.795	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.