TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32528	97807;97808;97809	chr2:178541495;178541494;178541493	chr2:179406222;179406221;179406220
N2AB	30887	92884;92885;92886	chr2:178541495;178541494;178541493	chr2:179406222;179406221;179406220
N2A	29960	90103;90104;90105	chr2:178541495;178541494;178541493	chr2:179406222;179406221;179406220
N2B	23463	70612;70613;70614	chr2:178541495;178541494;178541493	chr2:179406222;179406221;179406220
Novex-1	23588	70987;70988;70989	chr2:178541495;178541494;178541493	chr2:179406222;179406221;179406220
Novex-2	23655	71188;71189;71190	chr2:178541495;178541494;178541493	chr2:179406222;179406221;179406220
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: Fn3-125
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5876
• 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/R	None	None	0.999	N	0.815	0.458	0.715157034389	gnomAD-4.0.0	6.84387E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99632E-07	0	0
G/V	None	None	0.999	D	0.799	0.423	0.81923583777	gnomAD-4.0.0	1.36879E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31997E-05	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	0.3998	ambiguous	0.4263	ambiguous	-0.153	Destabilizing	0.995	D	0.577	neutral	N	0.485744192	None	None	I
G/C	0.4581	ambiguous	0.5188	ambiguous	-0.82	Destabilizing	1.0	D	0.827	deleterious	D	0.529336216	None	None	I
G/D	0.3103	likely_benign	0.4001	ambiguous	-0.546	Destabilizing	0.604	D	0.569	neutral	N	0.505445063	None	None	I
G/E	0.4476	ambiguous	0.5434	ambiguous	-0.709	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
G/F	0.8157	likely_pathogenic	0.8388	pathogenic	-0.993	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/H	0.5886	likely_pathogenic	0.6485	pathogenic	-0.295	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/I	0.7757	likely_pathogenic	0.8135	pathogenic	-0.434	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
G/K	0.6068	likely_pathogenic	0.6784	pathogenic	-0.466	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	I
G/L	0.7388	likely_pathogenic	0.7626	pathogenic	-0.434	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	I
G/M	0.7857	likely_pathogenic	0.81	pathogenic	-0.457	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/N	0.4091	ambiguous	0.4513	ambiguous	-0.203	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	I
G/P	0.979	likely_pathogenic	0.982	pathogenic	-0.316	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
G/Q	0.5116	ambiguous	0.585	pathogenic	-0.487	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	I
G/R	0.4824	ambiguous	0.5515	ambiguous	-0.071	Destabilizing	0.999	D	0.815	deleterious	N	0.498127682	None	None	I
G/S	0.2106	likely_benign	0.2277	benign	-0.318	Destabilizing	0.999	D	0.687	prob.neutral	N	0.487274675	None	None	I
G/T	0.5539	ambiguous	0.585	pathogenic	-0.42	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	I
G/V	0.7005	likely_pathogenic	0.7463	pathogenic	-0.316	Destabilizing	0.999	D	0.799	deleterious	D	0.528322258	None	None	I
G/W	0.7651	likely_pathogenic	0.8129	pathogenic	-1.099	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/Y	0.6829	likely_pathogenic	0.7264	pathogenic	-0.765	Destabilizing	1.0	D	0.809	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.