TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14341	43246;43247;43248	chr2:178633252;178633251;178633250	chr2:179497979;179497978;179497977
N2AB	12700	38323;38324;38325	chr2:178633252;178633251;178633250	chr2:179497979;179497978;179497977
N2A	11773	35542;35543;35544	chr2:178633252;178633251;178633250	chr2:179497979;179497978;179497977
N2B	5276	16051;16052;16053	chr2:178633252;178633251;178633250	chr2:179497979;179497978;179497977
Novex-1	5401	16426;16427;16428	chr2:178633252;178633251;178633250	chr2:179497979;179497978;179497977
Novex-2	5468	16627;16628;16629	chr2:178633252;178633251;178633250	chr2:179497979;179497978;179497977
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-94
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1563
• 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/G	rs1307501867	None	0.974	D	0.703	0.365	0.265010934533	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.3108	likely_benign	0.2466	benign	-1.25	Destabilizing	0.914	D	0.642	neutral	D	0.62863881	None	None	N
E/C	0.9285	likely_pathogenic	0.9089	pathogenic	-1.029	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/D	0.7223	likely_pathogenic	0.6605	pathogenic	-1.73	Destabilizing	0.914	D	0.499	neutral	D	0.554443047	None	None	N
E/F	0.8929	likely_pathogenic	0.8547	pathogenic	-1.091	Destabilizing	0.99	D	0.818	deleterious	None	None	None	None	N
E/G	0.5665	likely_pathogenic	0.5003	ambiguous	-1.621	Destabilizing	0.974	D	0.703	prob.delet.	D	0.63126318	None	None	N
E/H	0.8078	likely_pathogenic	0.7647	pathogenic	-1.364	Destabilizing	0.092	N	0.341	neutral	None	None	None	None	N
E/I	0.4473	ambiguous	0.393	ambiguous	-0.217	Destabilizing	0.99	D	0.833	deleterious	None	None	None	None	N
E/K	0.4851	ambiguous	0.4222	ambiguous	-1.613	Destabilizing	0.914	D	0.511	neutral	D	0.58974306	None	None	N
E/L	0.6578	likely_pathogenic	0.5802	pathogenic	-0.217	Destabilizing	0.98	D	0.789	deleterious	None	None	None	None	N
E/M	0.624	likely_pathogenic	0.5561	ambiguous	0.362	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/N	0.765	likely_pathogenic	0.6923	pathogenic	-1.815	Destabilizing	0.98	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.9893	likely_pathogenic	0.9893	pathogenic	-0.543	Destabilizing	0.997	D	0.816	deleterious	None	None	None	None	N
E/Q	0.2454	likely_benign	0.2125	benign	-1.612	Destabilizing	0.974	D	0.665	prob.neutral	N	0.500934651	None	None	N
E/R	0.6013	likely_pathogenic	0.5554	ambiguous	-1.434	Destabilizing	0.98	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.4559	ambiguous	0.3789	ambiguous	-2.346	Highly Destabilizing	0.933	D	0.622	neutral	None	None	None	None	N
E/T	0.377	ambiguous	0.3158	benign	-2.021	Highly Destabilizing	0.99	D	0.765	deleterious	None	None	None	None	N
E/V	0.2999	likely_benign	0.2587	benign	-0.543	Destabilizing	0.987	D	0.781	deleterious	D	0.566358545	None	None	N
E/W	0.9763	likely_pathogenic	0.9697	pathogenic	-1.155	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/Y	0.8941	likely_pathogenic	0.8573	pathogenic	-0.94	Destabilizing	0.961	D	0.795	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.