TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32863	98812;98813;98814	chr2:178539478;178539477;178539476	chr2:179404205;179404204;179404203
N2AB	31222	93889;93890;93891	chr2:178539478;178539477;178539476	chr2:179404205;179404204;179404203
N2A	30295	91108;91109;91110	chr2:178539478;178539477;178539476	chr2:179404205;179404204;179404203
N2B	23798	71617;71618;71619	chr2:178539478;178539477;178539476	chr2:179404205;179404204;179404203
Novex-1	23923	71992;71993;71994	chr2:178539478;178539477;178539476	chr2:179404205;179404204;179404203
Novex-2	23990	72193;72194;72195	chr2:178539478;178539477;178539476	chr2:179404205;179404204;179404203
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: Fn3-127
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.5356
• 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	rs746957606	-0.325	1.0	N	0.812	0.504	0.559581285787	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
N/Y	rs746957606	-0.325	1.0	N	0.812	0.504	0.559581285787	gnomAD-4.0.0	2.05255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	0	3.31301E-05

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	0.4516	ambiguous	0.409	ambiguous	-0.313	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
N/C	0.6312	likely_pathogenic	0.5872	pathogenic	0.25	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
N/D	0.1881	likely_benign	0.1789	benign	0.096	Stabilizing	0.999	D	0.703	prob.neutral	N	0.468263412	None	None	N
N/E	0.5566	ambiguous	0.5326	ambiguous	0.074	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
N/F	0.7844	likely_pathogenic	0.7535	pathogenic	-0.558	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
N/G	0.2497	likely_benign	0.2421	benign	-0.509	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
N/H	0.227	likely_benign	0.2108	benign	-0.448	Destabilizing	1.0	D	0.792	deleterious	N	0.514035774	None	None	N
N/I	0.6663	likely_pathogenic	0.6199	pathogenic	0.119	Stabilizing	1.0	D	0.826	deleterious	N	0.508439895	None	None	N
N/K	0.4733	ambiguous	0.4572	ambiguous	0.03	Stabilizing	1.0	D	0.805	deleterious	N	0.520943104	None	None	N
N/L	0.5568	ambiguous	0.5175	ambiguous	0.119	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/M	0.5733	likely_pathogenic	0.5224	ambiguous	0.345	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
N/P	0.9403	likely_pathogenic	0.9279	pathogenic	0.003	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
N/Q	0.5373	ambiguous	0.5085	ambiguous	-0.436	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
N/R	0.5819	likely_pathogenic	0.5614	ambiguous	0.101	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
N/S	0.1736	likely_benign	0.1607	benign	-0.235	Destabilizing	0.999	D	0.645	neutral	N	0.514862493	None	None	N
N/T	0.3025	likely_benign	0.271	benign	-0.111	Destabilizing	0.999	D	0.794	deleterious	N	0.484802232	None	None	N
N/V	0.6574	likely_pathogenic	0.6124	pathogenic	0.003	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/W	0.9178	likely_pathogenic	0.9008	pathogenic	-0.512	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
N/Y	0.3411	ambiguous	0.3103	benign	-0.264	Destabilizing	1.0	D	0.812	deleterious	N	0.496970166	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.