TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33421	100486;100487;100488	chr2:178536486;178536485;178536484	chr2:179401213;179401212;179401211
N2AB	31780	95563;95564;95565	chr2:178536486;178536485;178536484	chr2:179401213;179401212;179401211
N2A	30853	92782;92783;92784	chr2:178536486;178536485;178536484	chr2:179401213;179401212;179401211
N2B	24356	73291;73292;73293	chr2:178536486;178536485;178536484	chr2:179401213;179401212;179401211
Novex-1	24481	73666;73667;73668	chr2:178536486;178536485;178536484	chr2:179401213;179401212;179401211
Novex-2	24548	73867;73868;73869	chr2:178536486;178536485;178536484	chr2:179401213;179401212;179401211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-131
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.622
• 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
G/D	None	None	0.45	N	0.575	0.468	0.531342499125	gnomAD-4.0.0	7.01735E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.14506E-07	0	0
G/V	None	None	0.999	D	0.828	0.597	0.73341489499	gnomAD-4.0.0	7.01734E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.14506E-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
G/A	0.675	likely_pathogenic	0.7192	pathogenic	-0.2	Destabilizing	0.991	D	0.605	neutral	N	0.500007922	None	None	I
G/C	0.7765	likely_pathogenic	0.8369	pathogenic	-0.871	Destabilizing	1.0	D	0.833	deleterious	D	0.52424147	None	None	I
G/D	0.8097	likely_pathogenic	0.8691	pathogenic	-0.506	Destabilizing	0.45	N	0.575	neutral	N	0.514833721	None	None	I
G/E	0.8595	likely_pathogenic	0.9024	pathogenic	-0.661	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	I
G/F	0.9537	likely_pathogenic	0.9648	pathogenic	-0.997	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/H	0.9121	likely_pathogenic	0.9426	pathogenic	-0.305	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/I	0.9294	likely_pathogenic	0.9364	pathogenic	-0.477	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/K	0.8805	likely_pathogenic	0.9209	pathogenic	-0.473	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	I
G/L	0.9296	likely_pathogenic	0.9391	pathogenic	-0.477	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	I
G/M	0.9432	likely_pathogenic	0.9515	pathogenic	-0.522	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/N	0.7715	likely_pathogenic	0.8281	pathogenic	-0.229	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	I
G/P	0.9946	likely_pathogenic	0.9939	pathogenic	-0.361	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	I
G/Q	0.8562	likely_pathogenic	0.9016	pathogenic	-0.494	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	I
G/R	0.8214	likely_pathogenic	0.8729	pathogenic	-0.095	Destabilizing	0.999	D	0.834	deleterious	N	0.5153407	None	None	I
G/S	0.4797	ambiguous	0.5357	ambiguous	-0.364	Destabilizing	0.997	D	0.723	prob.delet.	N	0.49079121	None	None	I
G/T	0.8178	likely_pathogenic	0.8432	pathogenic	-0.457	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	I
G/V	0.8955	likely_pathogenic	0.9061	pathogenic	-0.361	Destabilizing	0.999	D	0.828	deleterious	D	0.530989419	None	None	I
G/W	0.9464	likely_pathogenic	0.9619	pathogenic	-1.091	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/Y	0.9273	likely_pathogenic	0.9503	pathogenic	-0.773	Destabilizing	1.0	D	0.821	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.