TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28745	86458;86459;86460	chr2:178559899;178559898;178559897	chr2:179424626;179424625;179424624
N2AB	27104	81535;81536;81537	chr2:178559899;178559898;178559897	chr2:179424626;179424625;179424624
N2A	26177	78754;78755;78756	chr2:178559899;178559898;178559897	chr2:179424626;179424625;179424624
N2B	19680	59263;59264;59265	chr2:178559899;178559898;178559897	chr2:179424626;179424625;179424624
Novex-1	19805	59638;59639;59640	chr2:178559899;178559898;178559897	chr2:179424626;179424625;179424624
Novex-2	19872	59839;59840;59841	chr2:178559899;178559898;178559897	chr2:179424626;179424625;179424624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-97
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0816
• 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
A/E	None	-2.582	0.931	N	0.69	0.225	0.529011059296	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/E	None	-2.582	0.931	N	0.69	0.225	0.529011059296	gnomAD-4.0.0	6.84387E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15977E-05	0
A/G	rs377367951	-1.802	0.792	N	0.53	0.207	None	gnomAD-2.1.1	3.58E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.41799E-04	3.13E-05	0
A/G	rs377367951	-1.802	0.792	N	0.53	0.207	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	2.82646E-04	0	2.94E-05	0	0
A/G	rs377367951	-1.802	0.792	N	0.53	0.207	None	gnomAD-4.0.0	4.15309E-05	None	None	None	None	N	None	1.3359E-05	0	None	0	0	None	1.56882E-04	0	4.49252E-05	0	4.80338E-05
A/T	rs1423142304	-1.723	0.027	N	0.342	0.157	0.272205846399	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/T	rs1423142304	-1.723	0.027	N	0.342	0.157	0.272205846399	gnomAD-4.0.0	6.36855E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73394E-05	0
A/V	rs377367951	-0.61	0.027	N	0.347	0.115	0.385417323374	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
A/V	rs377367951	-0.61	0.027	N	0.347	0.115	0.385417323374	gnomAD-4.0.0	1.09502E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.43921E-05	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
A/C	0.5642	likely_pathogenic	0.5914	pathogenic	-2.251	Highly Destabilizing	0.998	D	0.705	prob.delet.	None	None	None	None	N
A/D	0.9871	likely_pathogenic	0.988	pathogenic	-3.095	Highly Destabilizing	0.947	D	0.759	deleterious	None	None	None	None	N
A/E	0.965	likely_pathogenic	0.9711	pathogenic	-2.924	Highly Destabilizing	0.931	D	0.69	prob.delet.	N	0.473517924	None	None	N
A/F	0.8908	likely_pathogenic	0.8995	pathogenic	-0.916	Destabilizing	0.947	D	0.751	deleterious	None	None	None	None	N
A/G	0.4577	ambiguous	0.419	ambiguous	-1.733	Destabilizing	0.792	D	0.53	neutral	N	0.485381208	None	None	N
A/H	0.9837	likely_pathogenic	0.986	pathogenic	-1.668	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
A/I	0.3882	ambiguous	0.489	ambiguous	-0.422	Destabilizing	0.466	N	0.648	neutral	None	None	None	None	N
A/K	0.9886	likely_pathogenic	0.991	pathogenic	-1.448	Destabilizing	0.947	D	0.677	prob.neutral	None	None	None	None	N
A/L	0.3932	ambiguous	0.4386	ambiguous	-0.422	Destabilizing	0.717	D	0.572	neutral	None	None	None	None	N
A/M	0.5975	likely_pathogenic	0.6391	pathogenic	-1.123	Destabilizing	0.993	D	0.727	deleterious	None	None	None	None	N
A/N	0.9345	likely_pathogenic	0.9402	pathogenic	-1.927	Destabilizing	0.947	D	0.748	deleterious	None	None	None	None	N
A/P	0.2952	likely_benign	0.3254	benign	-0.706	Destabilizing	0.964	D	0.719	prob.delet.	N	0.504893429	None	None	N
A/Q	0.9413	likely_pathogenic	0.9506	pathogenic	-1.83	Destabilizing	0.973	D	0.685	prob.delet.	None	None	None	None	N
A/R	0.9665	likely_pathogenic	0.9725	pathogenic	-1.401	Destabilizing	0.947	D	0.693	prob.delet.	None	None	None	None	N
A/S	0.2631	likely_benign	0.2624	benign	-2.225	Highly Destabilizing	0.657	D	0.514	neutral	N	0.48462074	None	None	N
A/T	0.2628	likely_benign	0.29	benign	-1.95	Destabilizing	0.027	N	0.342	neutral	N	0.485462306	None	None	N
A/V	0.1595	likely_benign	0.2372	benign	-0.706	Destabilizing	0.027	N	0.347	neutral	N	0.480344488	None	None	N
A/W	0.9894	likely_pathogenic	0.9902	pathogenic	-1.444	Destabilizing	0.998	D	0.729	deleterious	None	None	None	None	N
A/Y	0.9713	likely_pathogenic	0.973	pathogenic	-1.042	Destabilizing	0.973	D	0.752	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.