TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21823	65692;65693;65694	chr2:178583715;178583714;178583713	chr2:179448442;179448441;179448440
N2AB	20182	60769;60770;60771	chr2:178583715;178583714;178583713	chr2:179448442;179448441;179448440
N2A	19255	57988;57989;57990	chr2:178583715;178583714;178583713	chr2:179448442;179448441;179448440
N2B	12758	38497;38498;38499	chr2:178583715;178583714;178583713	chr2:179448442;179448441;179448440
Novex-1	12883	38872;38873;38874	chr2:178583715;178583714;178583713	chr2:179448442;179448441;179448440
Novex-2	12950	39073;39074;39075	chr2:178583715;178583714;178583713	chr2:179448442;179448441;179448440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-46
• Domain position: 67
• Structural Position: 96
• Q(SASA): 0.5382
• 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
G/D	None	None	0.235	N	0.312	0.215	0.168933306366	gnomAD-4.0.0	1.59466E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88523E-05	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
G/A	0.1582	likely_benign	0.1452	benign	-0.221	Destabilizing	0.977	D	0.577	neutral	N	0.491932256	None	None	N
G/C	0.2546	likely_benign	0.2425	benign	-0.882	Destabilizing	1.0	D	0.737	prob.delet.	D	0.527433204	None	None	N
G/D	0.1535	likely_benign	0.1563	benign	-0.393	Destabilizing	0.235	N	0.312	neutral	N	0.506165652	None	None	N
G/E	0.2308	likely_benign	0.2229	benign	-0.55	Destabilizing	0.635	D	0.374	neutral	None	None	None	None	N
G/F	0.5792	likely_pathogenic	0.5485	ambiguous	-0.946	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
G/H	0.3526	ambiguous	0.3508	ambiguous	-0.406	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
G/I	0.416	ambiguous	0.3735	ambiguous	-0.386	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
G/K	0.4861	ambiguous	0.4645	ambiguous	-0.686	Destabilizing	0.995	D	0.758	deleterious	None	None	None	None	N
G/L	0.4643	ambiguous	0.4335	ambiguous	-0.386	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
G/M	0.5043	ambiguous	0.4686	ambiguous	-0.523	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/N	0.1842	likely_benign	0.1758	benign	-0.365	Destabilizing	0.99	D	0.749	deleterious	None	None	None	None	N
G/P	0.8758	likely_pathogenic	0.8612	pathogenic	-0.3	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
G/Q	0.3265	likely_benign	0.317	benign	-0.619	Destabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
G/R	0.3662	ambiguous	0.3653	ambiguous	-0.283	Destabilizing	0.993	D	0.757	deleterious	N	0.473979359	None	None	N
G/S	0.1038	likely_benign	0.1	benign	-0.528	Destabilizing	0.977	D	0.685	prob.neutral	N	0.475523068	None	None	N
G/T	0.2054	likely_benign	0.1863	benign	-0.609	Destabilizing	0.995	D	0.748	deleterious	None	None	None	None	N
G/V	0.298	likely_benign	0.2697	benign	-0.3	Destabilizing	0.997	D	0.743	deleterious	D	0.527179714	None	None	N
G/W	0.475	ambiguous	0.4895	ambiguous	-1.093	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
G/Y	0.4605	ambiguous	0.4352	ambiguous	-0.743	Destabilizing	1.0	D	0.769	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.