TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6031	18316;18317;18318	chr2:178730309;178730308;178730307	chr2:179595036;179595035;179595034
N2AB	5714	17365;17366;17367	chr2:178730309;178730308;178730307	chr2:179595036;179595035;179595034
N2A	4787	14584;14585;14586	chr2:178730309;178730308;178730307	chr2:179595036;179595035;179595034
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-44
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1605
• 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
L/F	rs775101958	-1.647	0.001	N	0.278	0.215	0.432604763906	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
L/F	rs775101958	-1.647	0.001	N	0.278	0.215	0.432604763906	gnomAD-4.0.0	1.59601E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4393E-05	0
L/I	None	None	0.201	D	0.624	0.209	0.486209434461	gnomAD-4.0.0	4.79587E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.30142E-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
L/A	0.8454	likely_pathogenic	0.8634	pathogenic	-2.771	Highly Destabilizing	0.4	N	0.667	neutral	None	None	None	None	N
L/C	0.7119	likely_pathogenic	0.729	pathogenic	-2.074	Highly Destabilizing	0.992	D	0.762	deleterious	None	None	None	None	N
L/D	0.9878	likely_pathogenic	0.9897	pathogenic	-3.359	Highly Destabilizing	0.972	D	0.857	deleterious	None	None	None	None	N
L/E	0.9417	likely_pathogenic	0.9471	pathogenic	-3.049	Highly Destabilizing	0.92	D	0.82	deleterious	None	None	None	None	N
L/F	0.0591	likely_benign	0.0579	benign	-1.613	Destabilizing	0.001	N	0.278	neutral	N	0.465199756	None	None	N
L/G	0.9371	likely_pathogenic	0.9422	pathogenic	-3.398	Highly Destabilizing	0.92	D	0.815	deleterious	None	None	None	None	N
L/H	0.7501	likely_pathogenic	0.757	pathogenic	-2.979	Highly Destabilizing	0.992	D	0.849	deleterious	None	None	None	None	N
L/I	0.1402	likely_benign	0.1496	benign	-0.906	Destabilizing	0.201	N	0.624	neutral	D	0.53287281	None	None	N
L/K	0.9008	likely_pathogenic	0.9139	pathogenic	-2.182	Highly Destabilizing	0.92	D	0.812	deleterious	None	None	None	None	N
L/M	0.115	likely_benign	0.1138	benign	-0.998	Destabilizing	0.127	N	0.43	neutral	None	None	None	None	N
L/N	0.9431	likely_pathogenic	0.9491	pathogenic	-2.779	Highly Destabilizing	0.972	D	0.859	deleterious	None	None	None	None	N
L/P	0.9732	likely_pathogenic	0.9781	pathogenic	-1.515	Destabilizing	0.972	D	0.859	deleterious	None	None	None	None	N
L/Q	0.751	likely_pathogenic	0.7641	pathogenic	-2.484	Highly Destabilizing	0.92	D	0.841	deleterious	None	None	None	None	N
L/R	0.839	likely_pathogenic	0.8534	pathogenic	-2.12	Highly Destabilizing	0.92	D	0.833	deleterious	None	None	None	None	N
L/S	0.9294	likely_pathogenic	0.9392	pathogenic	-3.449	Highly Destabilizing	0.712	D	0.771	deleterious	D	0.616844975	None	None	N
L/T	0.878	likely_pathogenic	0.8917	pathogenic	-2.97	Highly Destabilizing	0.617	D	0.71	prob.delet.	None	None	None	None	N
L/V	0.2177	likely_benign	0.2305	benign	-1.515	Destabilizing	0.201	N	0.667	neutral	D	0.567545706	None	None	N
L/W	0.2691	likely_benign	0.2628	benign	-2.054	Highly Destabilizing	0.992	D	0.828	deleterious	None	None	None	None	N
L/Y	0.3931	ambiguous	0.3769	ambiguous	-1.788	Destabilizing	0.447	N	0.681	prob.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.