TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18531	55816;55817;55818	chr2:178601406;178601405;178601404	chr2:179466133;179466132;179466131
N2AB	16890	50893;50894;50895	chr2:178601406;178601405;178601404	chr2:179466133;179466132;179466131
N2A	15963	48112;48113;48114	chr2:178601406;178601405;178601404	chr2:179466133;179466132;179466131
N2B	9466	28621;28622;28623	chr2:178601406;178601405;178601404	chr2:179466133;179466132;179466131
Novex-1	9591	28996;28997;28998	chr2:178601406;178601405;178601404	chr2:179466133;179466132;179466131
Novex-2	9658	29197;29198;29199	chr2:178601406;178601405;178601404	chr2:179466133;179466132;179466131
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-22
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.3635
• 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
P/T	None	None	0.01	N	0.177	0.136	0.199424873507	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	2.625E-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
P/A	0.0748	likely_benign	0.0722	benign	-0.794	Destabilizing	0.001	N	0.15	neutral	N	0.406020088	None	None	N
P/C	0.4331	ambiguous	0.4971	ambiguous	-0.625	Destabilizing	0.944	D	0.352	neutral	None	None	None	None	N
P/D	0.4307	ambiguous	0.4747	ambiguous	-0.632	Destabilizing	0.704	D	0.317	neutral	None	None	None	None	N
P/E	0.2953	likely_benign	0.3183	benign	-0.738	Destabilizing	0.495	N	0.329	neutral	None	None	None	None	N
P/F	0.5144	ambiguous	0.6056	pathogenic	-0.933	Destabilizing	0.944	D	0.381	neutral	None	None	None	None	N
P/G	0.2416	likely_benign	0.2554	benign	-0.973	Destabilizing	0.329	N	0.312	neutral	None	None	None	None	N
P/H	0.2015	likely_benign	0.2462	benign	-0.522	Destabilizing	0.981	D	0.321	neutral	None	None	None	None	N
P/I	0.2983	likely_benign	0.3332	benign	-0.461	Destabilizing	0.704	D	0.421	neutral	None	None	None	None	N
P/K	0.2757	likely_benign	0.342	ambiguous	-0.666	Destabilizing	0.704	D	0.329	neutral	None	None	None	None	N
P/L	0.1369	likely_benign	0.1544	benign	-0.461	Destabilizing	0.425	N	0.341	neutral	N	0.485248876	None	None	N
P/M	0.2808	likely_benign	0.3112	benign	-0.327	Destabilizing	0.981	D	0.335	neutral	None	None	None	None	N
P/N	0.2888	likely_benign	0.3045	benign	-0.331	Destabilizing	0.704	D	0.353	neutral	None	None	None	None	N
P/Q	0.1611	likely_benign	0.1838	benign	-0.617	Destabilizing	0.784	D	0.408	neutral	N	0.458566493	None	None	N
P/R	0.1909	likely_benign	0.2558	benign	-0.073	Destabilizing	0.642	D	0.378	neutral	N	0.423856487	None	None	N
P/S	0.1151	likely_benign	0.118	benign	-0.721	Destabilizing	0.01	N	0.163	neutral	N	0.415218361	None	None	N
P/T	0.0907	likely_benign	0.0926	benign	-0.727	Destabilizing	0.01	N	0.177	neutral	N	0.420624181	None	None	N
P/V	0.1796	likely_benign	0.1979	benign	-0.536	Destabilizing	0.329	N	0.312	neutral	None	None	None	None	N
P/W	0.6412	likely_pathogenic	0.7345	pathogenic	-1.005	Destabilizing	0.995	D	0.396	neutral	None	None	None	None	N
P/Y	0.448	ambiguous	0.5226	ambiguous	-0.716	Destabilizing	0.981	D	0.388	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.