TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21802	65629;65630;65631	chr2:178583778;178583777;178583776	chr2:179448505;179448504;179448503
N2AB	20161	60706;60707;60708	chr2:178583778;178583777;178583776	chr2:179448505;179448504;179448503
N2A	19234	57925;57926;57927	chr2:178583778;178583777;178583776	chr2:179448505;179448504;179448503
N2B	12737	38434;38435;38436	chr2:178583778;178583777;178583776	chr2:179448505;179448504;179448503
Novex-1	12862	38809;38810;38811	chr2:178583778;178583777;178583776	chr2:179448505;179448504;179448503
Novex-2	12929	39010;39011;39012	chr2:178583778;178583777;178583776	chr2:179448505;179448504;179448503
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-46
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0446
• 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
D/E	rs1228795197	-0.016	0.005	N	0.145	0.07	0.112648838833	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.34E-05	None	0	0	0
D/E	rs1228795197	-0.016	0.005	N	0.145	0.07	0.112648838833	gnomAD-4.0.0	1.59782E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44259E-05	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
D/A	0.2018	likely_benign	0.1645	benign	-0.008	Destabilizing	0.051	N	0.211	neutral	N	0.498796963	None	None	N
D/C	0.6428	likely_pathogenic	0.5738	pathogenic	-0.209	Destabilizing	0.998	D	0.345	neutral	None	None	None	None	N
D/E	0.131	likely_benign	0.108	benign	-0.221	Destabilizing	0.005	N	0.145	neutral	N	0.431723822	None	None	N
D/F	0.6517	likely_pathogenic	0.5731	pathogenic	-0.073	Destabilizing	0.991	D	0.308	neutral	None	None	None	None	N
D/G	0.1606	likely_benign	0.1294	benign	-0.117	Destabilizing	0.454	N	0.313	neutral	N	0.455272685	None	None	N
D/H	0.3768	ambiguous	0.2832	benign	0.561	Stabilizing	0.966	D	0.296	neutral	N	0.466342355	None	None	N
D/I	0.4843	ambiguous	0.3697	ambiguous	0.215	Stabilizing	0.974	D	0.329	neutral	None	None	None	None	N
D/K	0.3994	ambiguous	0.2706	benign	0.349	Stabilizing	0.728	D	0.31	neutral	None	None	None	None	N
D/L	0.436	ambiguous	0.338	benign	0.215	Stabilizing	0.842	D	0.342	neutral	None	None	None	None	N
D/M	0.609	likely_pathogenic	0.5121	ambiguous	-0.013	Destabilizing	0.998	D	0.312	neutral	None	None	None	None	N
D/N	0.1091	likely_benign	0.0881	benign	0.16	Stabilizing	0.012	N	0.234	neutral	N	0.477034824	None	None	N
D/P	0.7205	likely_pathogenic	0.5103	ambiguous	0.159	Stabilizing	0.974	D	0.318	neutral	None	None	None	None	N
D/Q	0.3097	likely_benign	0.2432	benign	0.164	Stabilizing	0.728	D	0.287	neutral	None	None	None	None	N
D/R	0.4814	ambiguous	0.3428	ambiguous	0.611	Stabilizing	0.949	D	0.312	neutral	None	None	None	None	N
D/S	0.1319	likely_benign	0.1082	benign	0.032	Stabilizing	0.525	D	0.304	neutral	None	None	None	None	N
D/T	0.2694	likely_benign	0.2036	benign	0.126	Stabilizing	0.842	D	0.289	neutral	None	None	None	None	N
D/V	0.2946	likely_benign	0.2257	benign	0.159	Stabilizing	0.801	D	0.319	neutral	N	0.483712867	None	None	N
D/W	0.8857	likely_pathogenic	0.8305	pathogenic	-0.025	Destabilizing	0.998	D	0.47	neutral	None	None	None	None	N
D/Y	0.3206	likely_benign	0.2637	benign	0.153	Stabilizing	0.989	D	0.306	neutral	N	0.504973574	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.