TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24190	72793;72794;72795	chr2:178573564;178573563;178573562	chr2:179438291;179438290;179438289
N2AB	22549	67870;67871;67872	chr2:178573564;178573563;178573562	chr2:179438291;179438290;179438289
N2A	21622	65089;65090;65091	chr2:178573564;178573563;178573562	chr2:179438291;179438290;179438289
N2B	15125	45598;45599;45600	chr2:178573564;178573563;178573562	chr2:179438291;179438290;179438289
Novex-1	15250	45973;45974;45975	chr2:178573564;178573563;178573562	chr2:179438291;179438290;179438289
Novex-2	15317	46174;46175;46176	chr2:178573564;178573563;178573562	chr2:179438291;179438290;179438289
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: Fn3-63
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.3672
• 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/V	rs1246622936	None	0.96	D	0.868	0.483	0.614967603648	gnomAD-4.0.0	7.43645E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.45217E-07	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	0.4773	ambiguous	0.5298	ambiguous	-0.395	Destabilizing	0.775	D	0.623	neutral	N	0.502548682	None	None	N
G/C	0.528	ambiguous	0.6012	pathogenic	-0.875	Destabilizing	0.995	D	0.856	deleterious	D	0.544735127	None	None	N
G/D	0.3011	likely_benign	0.326	benign	-0.675	Destabilizing	0.924	D	0.787	deleterious	N	0.520199316	None	None	N
G/E	0.5251	ambiguous	0.5669	pathogenic	-0.818	Destabilizing	0.941	D	0.859	deleterious	None	None	None	None	N
G/F	0.8882	likely_pathogenic	0.9095	pathogenic	-0.968	Destabilizing	0.996	D	0.869	deleterious	None	None	None	None	N
G/H	0.6846	likely_pathogenic	0.7213	pathogenic	-0.691	Destabilizing	0.996	D	0.853	deleterious	None	None	None	None	N
G/I	0.8956	likely_pathogenic	0.9184	pathogenic	-0.396	Destabilizing	0.992	D	0.868	deleterious	None	None	None	None	N
G/K	0.8066	likely_pathogenic	0.8395	pathogenic	-1.028	Destabilizing	0.941	D	0.862	deleterious	None	None	None	None	N
G/L	0.8584	likely_pathogenic	0.8897	pathogenic	-0.396	Destabilizing	0.97	D	0.861	deleterious	None	None	None	None	N
G/M	0.835	likely_pathogenic	0.8789	pathogenic	-0.427	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
G/N	0.2909	likely_benign	0.3134	benign	-0.634	Destabilizing	0.941	D	0.816	deleterious	None	None	None	None	N
G/P	0.99	likely_pathogenic	0.99	pathogenic	-0.359	Destabilizing	0.97	D	0.873	deleterious	None	None	None	None	N
G/Q	0.6456	likely_pathogenic	0.6889	pathogenic	-0.905	Destabilizing	0.992	D	0.878	deleterious	None	None	None	None	N
G/R	0.7339	likely_pathogenic	0.7744	pathogenic	-0.561	Destabilizing	0.96	D	0.88	deleterious	D	0.525363424	None	None	N
G/S	0.2208	likely_benign	0.2597	benign	-0.812	Destabilizing	0.048	N	0.645	neutral	N	0.506472248	None	None	N
G/T	0.5343	ambiguous	0.6174	pathogenic	-0.883	Destabilizing	0.941	D	0.854	deleterious	None	None	None	None	N
G/V	0.8094	likely_pathogenic	0.8425	pathogenic	-0.359	Destabilizing	0.96	D	0.868	deleterious	D	0.523655131	None	None	N
G/W	0.7519	likely_pathogenic	0.7969	pathogenic	-1.166	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
G/Y	0.717	likely_pathogenic	0.7587	pathogenic	-0.812	Destabilizing	0.996	D	0.864	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.