TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16642	50149;50150;50151	chr2:178612797;178612796;178612795	chr2:179477524;179477523;179477522
N2AB	15001	45226;45227;45228	chr2:178612797;178612796;178612795	chr2:179477524;179477523;179477522
N2A	14074	42445;42446;42447	chr2:178612797;178612796;178612795	chr2:179477524;179477523;179477522
N2B	7577	22954;22955;22956	chr2:178612797;178612796;178612795	chr2:179477524;179477523;179477522
Novex-1	7702	23329;23330;23331	chr2:178612797;178612796;178612795	chr2:179477524;179477523;179477522
Novex-2	7769	23530;23531;23532	chr2:178612797;178612796;178612795	chr2:179477524;179477523;179477522
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: Fn3-8
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.5152
• 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/L	rs2056587744	None	0.518	D	0.722	0.326	0.66200615542	gnomAD-4.0.0	1.59546E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86402E-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	0.1053	likely_benign	0.1253	benign	-0.495	Destabilizing	0.518	D	0.525	neutral	N	0.50415067	None	None	N
P/C	0.7468	likely_pathogenic	0.8041	pathogenic	-0.562	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
P/D	0.7121	likely_pathogenic	0.8127	pathogenic	-0.359	Destabilizing	0.909	D	0.627	neutral	None	None	None	None	N
P/E	0.5055	ambiguous	0.6207	pathogenic	-0.485	Destabilizing	0.909	D	0.638	neutral	None	None	None	None	N
P/F	0.7115	likely_pathogenic	0.8231	pathogenic	-0.805	Destabilizing	0.02	N	0.546	neutral	None	None	None	None	N
P/G	0.5427	ambiguous	0.6344	pathogenic	-0.622	Destabilizing	0.587	D	0.649	prob.neutral	None	None	None	None	N
P/H	0.3236	likely_benign	0.4579	ambiguous	-0.241	Destabilizing	0.983	D	0.771	deleterious	D	0.652520172	None	None	N
P/I	0.4319	ambiguous	0.5146	ambiguous	-0.315	Destabilizing	0.909	D	0.841	deleterious	None	None	None	None	N
P/K	0.4167	ambiguous	0.5473	ambiguous	-0.382	Destabilizing	0.833	D	0.632	neutral	None	None	None	None	N
P/L	0.2087	likely_benign	0.285	benign	-0.315	Destabilizing	0.518	D	0.722	deleterious	D	0.550940718	None	None	N
P/M	0.4907	ambiguous	0.5723	pathogenic	-0.245	Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	N
P/N	0.5816	likely_pathogenic	0.6689	pathogenic	-0.094	Destabilizing	0.833	D	0.837	deleterious	None	None	None	None	N
P/Q	0.2998	likely_benign	0.3891	ambiguous	-0.38	Destabilizing	0.909	D	0.683	prob.neutral	None	None	None	None	N
P/R	0.2488	likely_benign	0.393	ambiguous	0.159	Stabilizing	0.883	D	0.829	deleterious	D	0.527116637	None	None	N
P/S	0.2266	likely_benign	0.292	benign	-0.449	Destabilizing	0.062	N	0.362	neutral	N	0.503451938	None	None	N
P/T	0.1571	likely_benign	0.2064	benign	-0.476	Destabilizing	0.518	D	0.653	prob.neutral	D	0.558456859	None	None	N
P/V	0.2866	likely_benign	0.3421	ambiguous	-0.339	Destabilizing	0.909	D	0.636	neutral	None	None	None	None	N
P/W	0.88	likely_pathogenic	0.9419	pathogenic	-0.874	Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
P/Y	0.7105	likely_pathogenic	0.8234	pathogenic	-0.558	Destabilizing	0.833	D	0.846	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.