TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18592	55999;56000;56001	chr2:178601130;178601129;178601128	chr2:179465857;179465856;179465855
N2AB	16951	51076;51077;51078	chr2:178601130;178601129;178601128	chr2:179465857;179465856;179465855
N2A	16024	48295;48296;48297	chr2:178601130;178601129;178601128	chr2:179465857;179465856;179465855
N2B	9527	28804;28805;28806	chr2:178601130;178601129;178601128	chr2:179465857;179465856;179465855
Novex-1	9652	29179;29180;29181	chr2:178601130;178601129;178601128	chr2:179465857;179465856;179465855
Novex-2	9719	29380;29381;29382	chr2:178601130;178601129;178601128	chr2:179465857;179465856;179465855
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-23
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2054
• 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
T/A	None	None	0.999	N	0.503	0.495	0.253205268125	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.3543	ambiguous	0.3007	benign	-0.822	Destabilizing	0.999	D	0.503	neutral	N	0.471336467	None	None	N
T/C	0.8163	likely_pathogenic	0.7885	pathogenic	-0.676	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
T/D	0.7542	likely_pathogenic	0.6924	pathogenic	-0.957	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/E	0.7275	likely_pathogenic	0.6728	pathogenic	-0.897	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/F	0.8352	likely_pathogenic	0.7931	pathogenic	-0.692	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/G	0.3488	ambiguous	0.3231	benign	-1.14	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
T/H	0.6384	likely_pathogenic	0.5717	pathogenic	-1.433	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/I	0.9104	likely_pathogenic	0.8791	pathogenic	-0.048	Destabilizing	1.0	D	0.79	deleterious	N	0.505520742	None	None	N
T/K	0.5371	ambiguous	0.4814	ambiguous	-0.87	Destabilizing	1.0	D	0.797	deleterious	N	0.503938998	None	None	N
T/L	0.4886	ambiguous	0.429	ambiguous	-0.048	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
T/M	0.3692	ambiguous	0.3056	benign	0.157	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/N	0.3565	ambiguous	0.3009	benign	-1.08	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/P	0.8205	likely_pathogenic	0.7756	pathogenic	-0.273	Destabilizing	1.0	D	0.769	deleterious	N	0.512104107	None	None	N
T/Q	0.4956	ambiguous	0.437	ambiguous	-1.157	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/R	0.4626	ambiguous	0.394	ambiguous	-0.723	Destabilizing	1.0	D	0.771	deleterious	N	0.504939075	None	None	N
T/S	0.1758	likely_benign	0.1531	benign	-1.268	Destabilizing	0.999	D	0.527	neutral	N	0.464071101	None	None	N
T/V	0.7719	likely_pathogenic	0.7269	pathogenic	-0.273	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
T/W	0.947	likely_pathogenic	0.9316	pathogenic	-0.715	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
T/Y	0.8152	likely_pathogenic	0.7812	pathogenic	-0.435	Destabilizing	1.0	D	0.776	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.