TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22938	69037;69038;69039	chr2:178577614;178577613;178577612	chr2:179442341;179442340;179442339
N2AB	21297	64114;64115;64116	chr2:178577614;178577613;178577612	chr2:179442341;179442340;179442339
N2A	20370	61333;61334;61335	chr2:178577614;178577613;178577612	chr2:179442341;179442340;179442339
N2B	13873	41842;41843;41844	chr2:178577614;178577613;178577612	chr2:179442341;179442340;179442339
Novex-1	13998	42217;42218;42219	chr2:178577614;178577613;178577612	chr2:179442341;179442340;179442339
Novex-2	14065	42418;42419;42420	chr2:178577614;178577613;178577612	chr2:179442341;179442340;179442339
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: Fn3-54
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.5186
• 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/M	rs2046738934	None	0.994	N	0.634	0.302	0.298403945805	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/M	rs2046738934	None	0.994	N	0.634	0.302	0.298403945805	gnomAD-4.0.0	3.88038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.23917E-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	0.5684	likely_pathogenic	0.6425	pathogenic	-0.377	Destabilizing	0.797	D	0.543	neutral	None	None	None	None	N
K/C	0.7623	likely_pathogenic	0.817	pathogenic	-0.426	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
K/D	0.8408	likely_pathogenic	0.8842	pathogenic	-0.109	Destabilizing	0.965	D	0.651	prob.neutral	None	None	None	None	N
K/E	0.2784	likely_benign	0.32	benign	-0.043	Destabilizing	0.748	D	0.493	neutral	N	0.469212283	None	None	N
K/F	0.8997	likely_pathogenic	0.9271	pathogenic	-0.274	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
K/G	0.7292	likely_pathogenic	0.7939	pathogenic	-0.695	Destabilizing	0.965	D	0.582	neutral	None	None	None	None	N
K/H	0.3806	ambiguous	0.4251	ambiguous	-1.108	Destabilizing	0.99	D	0.637	neutral	None	None	None	None	N
K/I	0.5223	ambiguous	0.5838	pathogenic	0.419	Stabilizing	0.982	D	0.798	deleterious	None	None	None	None	N
K/L	0.5447	ambiguous	0.5934	pathogenic	0.419	Stabilizing	0.965	D	0.582	neutral	None	None	None	None	N
K/M	0.3626	ambiguous	0.4148	ambiguous	0.358	Stabilizing	0.994	D	0.634	neutral	N	0.469465773	None	None	N
K/N	0.6976	likely_pathogenic	0.7704	pathogenic	-0.231	Destabilizing	0.954	D	0.674	prob.neutral	N	0.503788178	None	None	N
K/P	0.9707	likely_pathogenic	0.9794	pathogenic	0.184	Stabilizing	0.982	D	0.675	prob.neutral	None	None	None	None	N
K/Q	0.1603	likely_benign	0.1788	benign	-0.388	Destabilizing	0.155	N	0.23	neutral	N	0.516302501	None	None	N
K/R	0.0831	likely_benign	0.0864	benign	-0.466	Destabilizing	0.748	D	0.539	neutral	N	0.463486737	None	None	N
K/S	0.6272	likely_pathogenic	0.6987	pathogenic	-0.838	Destabilizing	0.797	D	0.619	neutral	None	None	None	None	N
K/T	0.2859	likely_benign	0.3338	benign	-0.582	Destabilizing	0.954	D	0.655	prob.neutral	N	0.509373742	None	None	N
K/V	0.4697	ambiguous	0.5145	ambiguous	0.184	Stabilizing	0.965	D	0.708	prob.delet.	None	None	None	None	N
K/W	0.8585	likely_pathogenic	0.8912	pathogenic	-0.165	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8082	likely_pathogenic	0.8513	pathogenic	0.145	Stabilizing	0.982	D	0.757	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.