TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32602	98029;98030;98031	chr2:178540362;178540361;178540360	chr2:179405089;179405088;179405087
N2AB	30961	93106;93107;93108	chr2:178540362;178540361;178540360	chr2:179405089;179405088;179405087
N2A	30034	90325;90326;90327	chr2:178540362;178540361;178540360	chr2:179405089;179405088;179405087
N2B	23537	70834;70835;70836	chr2:178540362;178540361;178540360	chr2:179405089;179405088;179405087
Novex-1	23662	71209;71210;71211	chr2:178540362;178540361;178540360	chr2:179405089;179405088;179405087
Novex-2	23729	71410;71411;71412	chr2:178540362;178540361;178540360	chr2:179405089;179405088;179405087
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-126
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2247
• 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/E	None	None	0.999	N	0.818	0.315	0.496099317193	gnomAD-4.0.0	1.59773E-06	None	None	None	None	N	None	0	0	None	0	2.77562E-05	None	0	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	0.2172	likely_benign	0.237	benign	-0.821	Destabilizing	0.604	D	0.511	neutral	N	0.514614733	None	None	N
G/C	0.3723	ambiguous	0.3944	ambiguous	-1.26	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/D	0.5261	ambiguous	0.5648	pathogenic	-2.369	Highly Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
G/E	0.474	ambiguous	0.5037	ambiguous	-2.41	Highly Destabilizing	0.999	D	0.818	deleterious	N	0.482747862	None	None	N
G/F	0.8462	likely_pathogenic	0.8479	pathogenic	-1.191	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/H	0.6908	likely_pathogenic	0.7204	pathogenic	-1.282	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/I	0.7498	likely_pathogenic	0.762	pathogenic	-0.456	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/K	0.6642	likely_pathogenic	0.6883	pathogenic	-1.334	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
G/L	0.6987	likely_pathogenic	0.7119	pathogenic	-0.456	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
G/M	0.7657	likely_pathogenic	0.7815	pathogenic	-0.433	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/N	0.6149	likely_pathogenic	0.6396	pathogenic	-1.243	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
G/P	0.971	likely_pathogenic	0.9712	pathogenic	-0.54	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
G/Q	0.5617	ambiguous	0.5825	pathogenic	-1.495	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
G/R	0.5154	ambiguous	0.5563	ambiguous	-0.962	Destabilizing	0.999	D	0.847	deleterious	N	0.511020335	None	None	N
G/S	0.1409	likely_benign	0.1669	benign	-1.362	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
G/T	0.3594	ambiguous	0.3974	ambiguous	-1.349	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
G/V	0.5756	likely_pathogenic	0.5922	pathogenic	-0.54	Destabilizing	0.997	D	0.826	deleterious	N	0.511527314	None	None	N
G/W	0.7094	likely_pathogenic	0.7352	pathogenic	-1.56	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/Y	0.748	likely_pathogenic	0.7609	pathogenic	-1.153	Destabilizing	1.0	D	0.844	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.