TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32234	96925;96926;96927	chr2:178543273;178543272;178543271	chr2:179408000;179407999;179407998
N2AB	30593	92002;92003;92004	chr2:178543273;178543272;178543271	chr2:179408000;179407999;179407998
N2A	29666	89221;89222;89223	chr2:178543273;178543272;178543271	chr2:179408000;179407999;179407998
N2B	23169	69730;69731;69732	chr2:178543273;178543272;178543271	chr2:179408000;179407999;179407998
Novex-1	23294	70105;70106;70107	chr2:178543273;178543272;178543271	chr2:179408000;179407999;179407998
Novex-2	23361	70306;70307;70308	chr2:178543273;178543272;178543271	chr2:179408000;179407999;179407998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-123
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1496
• 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
L/H	None	None	1.0	N	0.827	0.666	0.817826572935	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.8252	likely_pathogenic	0.8337	pathogenic	-2.388	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	I
L/C	0.8171	likely_pathogenic	0.8046	pathogenic	-1.796	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
L/D	0.9897	likely_pathogenic	0.9897	pathogenic	-2.548	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
L/E	0.9335	likely_pathogenic	0.9372	pathogenic	-2.427	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
L/F	0.6633	likely_pathogenic	0.6246	pathogenic	-1.564	Destabilizing	1.0	D	0.794	deleterious	N	0.492511233	None	None	I
L/G	0.9491	likely_pathogenic	0.954	pathogenic	-2.842	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
L/H	0.9006	likely_pathogenic	0.8919	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.827	deleterious	N	0.495806597	None	None	I
L/I	0.1065	likely_benign	0.0939	benign	-1.127	Destabilizing	0.999	D	0.672	neutral	N	0.356916632	None	None	I
L/K	0.9001	likely_pathogenic	0.9136	pathogenic	-1.807	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
L/M	0.274	likely_benign	0.2402	benign	-1.028	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
L/N	0.9084	likely_pathogenic	0.9025	pathogenic	-1.904	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
L/P	0.6256	likely_pathogenic	0.7199	pathogenic	-1.523	Destabilizing	1.0	D	0.869	deleterious	N	0.518193587	None	None	I
L/Q	0.8113	likely_pathogenic	0.8101	pathogenic	-1.954	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
L/R	0.8686	likely_pathogenic	0.8882	pathogenic	-1.297	Destabilizing	1.0	D	0.891	deleterious	N	0.495806597	None	None	I
L/S	0.9359	likely_pathogenic	0.9309	pathogenic	-2.575	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
L/T	0.7907	likely_pathogenic	0.7837	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
L/V	0.138	likely_benign	0.1249	benign	-1.523	Destabilizing	0.999	D	0.665	neutral	N	0.420336179	None	None	I
L/W	0.8769	likely_pathogenic	0.8679	pathogenic	-1.832	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
L/Y	0.9023	likely_pathogenic	0.8941	pathogenic	-1.585	Destabilizing	1.0	D	0.859	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.