TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34187	102784;102785;102786	chr2:178534056;178534055;178534054	chr2:179398783;179398782;179398781
N2AB	32546	97861;97862;97863	chr2:178534056;178534055;178534054	chr2:179398783;179398782;179398781
N2A	31619	95080;95081;95082	chr2:178534056;178534055;178534054	chr2:179398783;179398782;179398781
N2B	25122	75589;75590;75591	chr2:178534056;178534055;178534054	chr2:179398783;179398782;179398781
Novex-1	25247	75964;75965;75966	chr2:178534056;178534055;178534054	chr2:179398783;179398782;179398781
Novex-2	25314	76165;76166;76167	chr2:178534056;178534055;178534054	chr2:179398783;179398782;179398781
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-160
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.1746
• 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
Y/C	rs1354824295	-0.677	1.0	N	0.805	0.588	0.652883116041	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	9.94E-05	0	None	0	None	0	0	0
Y/C	rs1354824295	-0.677	1.0	N	0.805	0.588	0.652883116041	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	4.76599E-05	0	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
Y/A	0.7878	likely_pathogenic	0.753	pathogenic	-1.828	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
Y/C	0.3497	ambiguous	0.3807	ambiguous	-0.759	Destabilizing	1.0	D	0.805	deleterious	N	0.521765115	None	None	N
Y/D	0.7024	likely_pathogenic	0.6649	pathogenic	-0.081	Destabilizing	1.0	D	0.808	deleterious	D	0.529056447	None	None	N
Y/E	0.8432	likely_pathogenic	0.8161	pathogenic	0.005	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/F	0.1386	likely_benign	0.1325	benign	-0.602	Destabilizing	0.999	D	0.689	prob.neutral	N	0.493866438	None	None	N
Y/G	0.7787	likely_pathogenic	0.7357	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
Y/H	0.395	ambiguous	0.3761	ambiguous	-0.624	Destabilizing	1.0	D	0.738	prob.delet.	N	0.497080101	None	None	N
Y/I	0.6863	likely_pathogenic	0.6727	pathogenic	-0.9	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
Y/K	0.801	likely_pathogenic	0.7689	pathogenic	-0.866	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
Y/L	0.6028	likely_pathogenic	0.5865	pathogenic	-0.9	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Y/M	0.725	likely_pathogenic	0.6967	pathogenic	-0.709	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/N	0.4661	ambiguous	0.4225	ambiguous	-1.2	Destabilizing	1.0	D	0.807	deleterious	N	0.490575416	None	None	N
Y/P	0.96	likely_pathogenic	0.9572	pathogenic	-1.201	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/Q	0.7801	likely_pathogenic	0.7549	pathogenic	-1.056	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/R	0.6559	likely_pathogenic	0.6186	pathogenic	-0.562	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Y/S	0.4349	ambiguous	0.388	ambiguous	-1.771	Destabilizing	1.0	D	0.809	deleterious	N	0.458599071	None	None	N
Y/T	0.6742	likely_pathogenic	0.6364	pathogenic	-1.586	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/V	0.5489	ambiguous	0.5374	ambiguous	-1.201	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
Y/W	0.4666	ambiguous	0.4566	ambiguous	-0.272	Destabilizing	1.0	D	0.719	prob.delet.	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.