TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17081	51466;51467;51468	chr2:178610285;178610284;178610283	chr2:179475012;179475011;179475010
N2AB	15440	46543;46544;46545	chr2:178610285;178610284;178610283	chr2:179475012;179475011;179475010
N2A	14513	43762;43763;43764	chr2:178610285;178610284;178610283	chr2:179475012;179475011;179475010
N2B	8016	24271;24272;24273	chr2:178610285;178610284;178610283	chr2:179475012;179475011;179475010
Novex-1	8141	24646;24647;24648	chr2:178610285;178610284;178610283	chr2:179475012;179475011;179475010
Novex-2	8208	24847;24848;24849	chr2:178610285;178610284;178610283	chr2:179475012;179475011;179475010
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-12
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.2066
• 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
H/P	None	None	0.997	D	0.683	0.482	0.602375283534	gnomAD-4.0.0	1.59302E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43349E-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
H/A	0.8461	likely_pathogenic	0.7555	pathogenic	-1.474	Destabilizing	0.971	D	0.61	neutral	None	None	None	None	N
H/C	0.5206	ambiguous	0.4167	ambiguous	-0.702	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
H/D	0.8374	likely_pathogenic	0.7763	pathogenic	-1.047	Destabilizing	0.98	D	0.568	neutral	N	0.479050103	None	None	N
H/E	0.9227	likely_pathogenic	0.8758	pathogenic	-0.897	Destabilizing	0.985	D	0.422	neutral	None	None	None	None	N
H/F	0.7619	likely_pathogenic	0.6837	pathogenic	0.065	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	N
H/G	0.7151	likely_pathogenic	0.5996	pathogenic	-1.855	Destabilizing	0.985	D	0.593	neutral	None	None	None	None	N
H/I	0.9761	likely_pathogenic	0.9576	pathogenic	-0.38	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
H/K	0.9049	likely_pathogenic	0.8417	pathogenic	-1.093	Destabilizing	0.985	D	0.571	neutral	None	None	None	None	N
H/L	0.7577	likely_pathogenic	0.6548	pathogenic	-0.38	Destabilizing	0.997	D	0.69	prob.neutral	N	0.468898298	None	None	N
H/M	0.942	likely_pathogenic	0.9063	pathogenic	-0.564	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
H/N	0.3396	likely_benign	0.2631	benign	-1.383	Destabilizing	0.98	D	0.434	neutral	N	0.445780461	None	None	N
H/P	0.9801	likely_pathogenic	0.9749	pathogenic	-0.73	Destabilizing	0.997	D	0.683	prob.neutral	D	0.601166596	None	None	N
H/Q	0.761	likely_pathogenic	0.6474	pathogenic	-1.053	Destabilizing	0.997	D	0.468	neutral	N	0.474331153	None	None	N
H/R	0.7077	likely_pathogenic	0.5765	pathogenic	-1.311	Destabilizing	0.997	D	0.46	neutral	N	0.47790411	None	None	N
H/S	0.5763	likely_pathogenic	0.4611	ambiguous	-1.553	Destabilizing	0.719	D	0.335	neutral	None	None	None	None	N
H/T	0.8786	likely_pathogenic	0.7941	pathogenic	-1.3	Destabilizing	0.971	D	0.617	neutral	None	None	None	None	N
H/V	0.954	likely_pathogenic	0.9183	pathogenic	-0.73	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
H/W	0.8541	likely_pathogenic	0.8086	pathogenic	0.518	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
H/Y	0.3254	likely_benign	0.2564	benign	0.489	Stabilizing	0.997	D	0.468	neutral	N	0.473566421	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.