TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10039	30340;30341;30342	chr2:178704255;178704254;178704253	chr2:179568982;179568981;179568980
N2AB	9722	29389;29390;29391	chr2:178704255;178704254;178704253	chr2:179568982;179568981;179568980
N2A	8795	26608;26609;26610	chr2:178704255;178704254;178704253	chr2:179568982;179568981;179568980
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-85
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.6892
• 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
E/K	None	None	0.003	None	0.113	0.188	0.265929055128	gnomAD-4.0.0	1.36828E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79879E-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
E/A	0.1971	likely_benign	0.239	benign	-0.268	Destabilizing	0.047	N	0.24	neutral	None	None	None	None	N
E/C	0.9336	likely_pathogenic	0.9573	pathogenic	-0.201	Destabilizing	0.983	D	0.247	neutral	None	None	None	None	N
E/D	0.2737	likely_benign	0.3521	ambiguous	-0.357	Destabilizing	0.101	N	0.161	neutral	None	None	None	None	N
E/F	0.8138	likely_pathogenic	0.8666	pathogenic	-0.096	Destabilizing	0.836	D	0.294	neutral	None	None	None	None	N
E/G	0.2854	likely_benign	0.3568	ambiguous	-0.461	Destabilizing	0.101	N	0.223	neutral	None	None	None	None	N
E/H	0.6438	likely_pathogenic	0.7202	pathogenic	0.283	Stabilizing	0.836	D	0.217	neutral	None	None	None	None	N
E/I	0.4467	ambiguous	0.5054	ambiguous	0.204	Stabilizing	0.264	N	0.356	neutral	None	None	None	None	N
E/K	0.2527	likely_benign	0.2993	benign	0.277	Stabilizing	0.003	N	0.113	neutral	None	None	None	None	N
E/L	0.5221	ambiguous	0.5847	pathogenic	0.204	Stabilizing	0.129	N	0.251	neutral	None	None	None	None	N
E/M	0.5793	likely_pathogenic	0.6418	pathogenic	0.11	Stabilizing	0.836	D	0.263	neutral	None	None	None	None	N
E/N	0.405	ambiguous	0.5117	ambiguous	-0.095	Destabilizing	0.001	N	0.113	neutral	None	None	None	None	N
E/P	0.9644	likely_pathogenic	0.9755	pathogenic	0.067	Stabilizing	0.593	D	0.283	neutral	None	None	None	None	N
E/Q	0.1953	likely_benign	0.2169	benign	-0.046	Destabilizing	0.021	N	0.237	neutral	None	None	None	None	N
E/R	0.4035	ambiguous	0.4748	ambiguous	0.566	Stabilizing	0.129	N	0.124	neutral	None	None	None	None	N
E/S	0.2616	likely_benign	0.335	benign	-0.241	Destabilizing	0.004	N	0.165	neutral	None	None	None	None	N
E/T	0.2925	likely_benign	0.3486	ambiguous	-0.081	Destabilizing	0.001	N	0.148	neutral	None	None	None	None	N
E/V	0.2935	likely_benign	0.3387	benign	0.067	Stabilizing	0.213	N	0.286	neutral	None	None	None	None	N
E/W	0.9441	likely_pathogenic	0.9635	pathogenic	0.044	Stabilizing	0.983	D	0.243	neutral	None	None	None	None	N
E/Y	0.7815	likely_pathogenic	0.8437	pathogenic	0.141	Stabilizing	0.836	D	0.323	neutral	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.