TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8286	25081;25082;25083	chr2:178718150;178718149;178718148	chr2:179582877;179582876;179582875
N2AB	7969	24130;24131;24132	chr2:178718150;178718149;178718148	chr2:179582877;179582876;179582875
N2A	7042	21349;21350;21351	chr2:178718150;178718149;178718148	chr2:179582877;179582876;179582875
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-68
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3835
• 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	rs1454054276	-0.78	0.114	N	0.456	0.158	0.236278675362	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/E	rs1454054276	-0.78	0.114	N	0.456	0.158	0.236278675362	gnomAD-4.0.0	3.50342E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.40793E-05	0	3.31543E-05
K/Q	rs1454054276	None	None	N	0.173	0.106	0.141422826196	gnomAD-4.0.0	1.37389E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.31543E-05
K/R	None	None	0.001	N	0.298	0.167	0.219573609325	gnomAD-4.0.0	6.86896E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99557E-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
K/A	0.3961	ambiguous	0.4419	ambiguous	-0.874	Destabilizing	0.363	N	0.457	neutral	None	None	None	None	N
K/C	0.7351	likely_pathogenic	0.7442	pathogenic	-0.997	Destabilizing	0.996	D	0.627	neutral	None	None	None	None	N
K/D	0.7542	likely_pathogenic	0.809	pathogenic	-0.942	Destabilizing	0.734	D	0.53	neutral	None	None	None	None	N
K/E	0.1793	likely_benign	0.1928	benign	-0.764	Destabilizing	0.114	N	0.456	neutral	N	0.466661194	None	None	N
K/F	0.7761	likely_pathogenic	0.7897	pathogenic	-0.23	Destabilizing	0.96	D	0.621	neutral	None	None	None	None	N
K/G	0.6623	likely_pathogenic	0.73	pathogenic	-1.313	Destabilizing	0.734	D	0.558	neutral	None	None	None	None	N
K/H	0.3102	likely_benign	0.3224	benign	-1.601	Destabilizing	0.801	D	0.589	neutral	None	None	None	None	N
K/I	0.2873	likely_benign	0.2845	benign	0.308	Stabilizing	0.303	N	0.62	neutral	D	0.526923006	None	None	N
K/L	0.3504	ambiguous	0.3559	ambiguous	0.308	Stabilizing	0.075	N	0.558	neutral	None	None	None	None	N
K/M	0.2064	likely_benign	0.208	benign	0.132	Stabilizing	0.701	D	0.59	neutral	None	None	None	None	N
K/N	0.4867	ambiguous	0.5581	ambiguous	-1.282	Destabilizing	0.675	D	0.471	neutral	D	0.529384521	None	None	N
K/P	0.9405	likely_pathogenic	0.9544	pathogenic	-0.058	Destabilizing	0.951	D	0.605	neutral	None	None	None	None	N
K/Q	0.1235	likely_benign	0.1206	benign	-1.19	Destabilizing	None	N	0.173	neutral	N	0.477243547	None	None	N
K/R	0.0839	likely_benign	0.0822	benign	-1.185	Destabilizing	0.001	N	0.298	neutral	N	0.502371278	None	None	N
K/S	0.4629	ambiguous	0.521	ambiguous	-1.847	Destabilizing	0.58	D	0.419	neutral	None	None	None	None	N
K/T	0.1588	likely_benign	0.1681	benign	-1.447	Destabilizing	0.385	N	0.53	neutral	N	0.514548354	None	None	N
K/V	0.2712	likely_benign	0.2619	benign	-0.058	Destabilizing	0.273	N	0.609	neutral	None	None	None	None	N
K/W	0.7958	likely_pathogenic	0.7884	pathogenic	-0.193	Destabilizing	0.997	D	0.647	neutral	None	None	None	None	N
K/Y	0.6411	likely_pathogenic	0.6638	pathogenic	0.097	Stabilizing	0.478	N	0.618	neutral	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.