TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16483	49672;49673;49674	chr2:178613836;178613835;178613834	chr2:179478563;179478562;179478561
N2AB	14842	44749;44750;44751	chr2:178613836;178613835;178613834	chr2:179478563;179478562;179478561
N2A	13915	41968;41969;41970	chr2:178613836;178613835;178613834	chr2:179478563;179478562;179478561
N2B	7418	22477;22478;22479	chr2:178613836;178613835;178613834	chr2:179478563;179478562;179478561
Novex-1	7543	22852;22853;22854	chr2:178613836;178613835;178613834	chr2:179478563;179478562;179478561
Novex-2	7610	23053;23054;23055	chr2:178613836;178613835;178613834	chr2:179478563;179478562;179478561
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: Fn3-7
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4892
• Predicted PPI site: I

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/K	rs1421106581	None	0.978	N	0.7	0.401	0.406257615169	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
T/K	rs1421106581	None	0.978	N	0.7	0.401	0.406257615169	gnomAD-4.0.0	6.58371E-06	None	None	None	None	I	None	2.41628E-05	0	None	0	0	None	0	0	0	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	0.2337	likely_benign	0.2182	benign	-0.61	Destabilizing	0.865	D	0.445	neutral	D	0.624106923	None	None	I
T/C	0.6907	likely_pathogenic	0.6441	pathogenic	-0.373	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
T/D	0.8564	likely_pathogenic	0.8361	pathogenic	0.09	Stabilizing	0.997	D	0.778	deleterious	None	None	None	None	I
T/E	0.7334	likely_pathogenic	0.7068	pathogenic	0.06	Stabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	I
T/F	0.6489	likely_pathogenic	0.5674	pathogenic	-0.786	Destabilizing	0.983	D	0.827	deleterious	None	None	None	None	I
T/G	0.6048	likely_pathogenic	0.5544	ambiguous	-0.828	Destabilizing	0.992	D	0.698	prob.neutral	None	None	None	None	I
T/H	0.653	likely_pathogenic	0.59	pathogenic	-1.1	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
T/I	0.2992	likely_benign	0.2676	benign	-0.136	Destabilizing	0.957	D	0.695	prob.neutral	N	0.504362558	None	None	I
T/K	0.4995	ambiguous	0.4666	ambiguous	-0.559	Destabilizing	0.978	D	0.7	prob.neutral	N	0.474552325	None	None	I
T/L	0.1497	likely_benign	0.1366	benign	-0.136	Destabilizing	0.745	D	0.528	neutral	None	None	None	None	I
T/M	0.15	likely_benign	0.1382	benign	0.1	Stabilizing	0.547	D	0.425	neutral	None	None	None	None	I
T/N	0.3797	ambiguous	0.3247	benign	-0.397	Destabilizing	0.992	D	0.685	prob.neutral	None	None	None	None	I
T/P	0.8001	likely_pathogenic	0.8424	pathogenic	-0.262	Destabilizing	0.996	D	0.786	deleterious	D	0.733511171	None	None	I
T/Q	0.5242	ambiguous	0.4646	ambiguous	-0.601	Destabilizing	0.992	D	0.789	deleterious	None	None	None	None	I
T/R	0.4547	ambiguous	0.4485	ambiguous	-0.304	Destabilizing	0.978	D	0.789	deleterious	D	0.563452151	None	None	I
T/S	0.2569	likely_benign	0.2231	benign	-0.686	Destabilizing	0.928	D	0.427	neutral	N	0.469033215	None	None	I
T/V	0.2529	likely_benign	0.2221	benign	-0.262	Destabilizing	0.895	D	0.45	neutral	None	None	None	None	I
T/W	0.9052	likely_pathogenic	0.8815	pathogenic	-0.718	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	I
T/Y	0.7222	likely_pathogenic	0.6743	pathogenic	-0.482	Destabilizing	0.992	D	0.835	deleterious	None	None	None	None	I

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.