TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21052	63379;63380;63381	chr2:178588571;178588570;178588569	chr2:179453298;179453297;179453296
N2AB	19411	58456;58457;58458	chr2:178588571;178588570;178588569	chr2:179453298;179453297;179453296
N2A	18484	55675;55676;55677	chr2:178588571;178588570;178588569	chr2:179453298;179453297;179453296
N2B	11987	36184;36185;36186	chr2:178588571;178588570;178588569	chr2:179453298;179453297;179453296
Novex-1	12112	36559;36560;36561	chr2:178588571;178588570;178588569	chr2:179453298;179453297;179453296
Novex-2	12179	36760;36761;36762	chr2:178588571;178588570;178588569	chr2:179453298;179453297;179453296
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-40
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.3605
• 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
P/L	None	None	0.995	N	0.724	0.372	0.541692676538	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.0985	likely_benign	0.0852	benign	-1.692	Destabilizing	0.429	N	0.408	neutral	N	0.494620507	None	None	I
P/C	0.6022	likely_pathogenic	0.5605	ambiguous	-1.029	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
P/D	0.8926	likely_pathogenic	0.8675	pathogenic	-1.478	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	I
P/E	0.6551	likely_pathogenic	0.593	pathogenic	-1.436	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
P/F	0.764	likely_pathogenic	0.7248	pathogenic	-1.242	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
P/G	0.6658	likely_pathogenic	0.577	pathogenic	-2.059	Highly Destabilizing	0.974	D	0.757	deleterious	None	None	None	None	I
P/H	0.635	likely_pathogenic	0.5816	pathogenic	-1.606	Destabilizing	1.0	D	0.817	deleterious	N	0.504752911	None	None	I
P/I	0.386	ambiguous	0.3738	ambiguous	-0.757	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	I
P/K	0.8374	likely_pathogenic	0.8038	pathogenic	-1.238	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	I
P/L	0.2443	likely_benign	0.2399	benign	-0.757	Destabilizing	0.995	D	0.724	deleterious	N	0.464110175	None	None	I
P/M	0.5113	ambiguous	0.475	ambiguous	-0.562	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
P/N	0.7917	likely_pathogenic	0.7291	pathogenic	-1.067	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	I
P/Q	0.5047	ambiguous	0.4511	ambiguous	-1.193	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	I
P/R	0.6982	likely_pathogenic	0.6678	pathogenic	-0.788	Destabilizing	0.998	D	0.849	deleterious	N	0.499219502	None	None	I
P/S	0.2849	likely_benign	0.2351	benign	-1.656	Destabilizing	0.99	D	0.744	deleterious	N	0.502778631	None	None	I
P/T	0.2473	likely_benign	0.2191	benign	-1.499	Destabilizing	0.995	D	0.716	prob.delet.	N	0.519132163	None	None	I
P/V	0.2547	likely_benign	0.2446	benign	-1.035	Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	I
P/W	0.9057	likely_pathogenic	0.8907	pathogenic	-1.482	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
P/Y	0.8044	likely_pathogenic	0.762	pathogenic	-1.176	Destabilizing	1.0	D	0.855	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.