TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4652	14179;14180;14181	chr2:178739279;178739278;178739277	chr2:179604006;179604005;179604004
N2AB	4335	13228;13229;13230	chr2:178739279;178739278;178739277	chr2:179604006;179604005;179604004
N2A	None	None	chr2:None	chr2:None
N2B	4289	13090;13091;13092	chr2:178739279;178739278;178739277	chr2:179604006;179604005;179604004
Novex-1	4414	13465;13466;13467	chr2:178739279;178739278;178739277	chr2:179604006;179604005;179604004
Novex-2	4481	13666;13667;13668	chr2:178739279;178739278;178739277	chr2:179604006;179604005;179604004
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-29
• Domain position: 47
• Structural Position: 123
• Q(SASA): 0.3185
• 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
C/Y	rs2082064227	None	1.0	N	0.855	0.489	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
C/Y	rs2082064227	None	1.0	N	0.855	0.489	None	gnomAD-4.0.0	6.57229E-06	None	None	None	None	N	None	2.41289E-05	0	None	0	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
C/A	0.5094	ambiguous	0.5647	pathogenic	-1.878	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
C/D	0.7184	likely_pathogenic	0.774	pathogenic	-0.155	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
C/E	0.7693	likely_pathogenic	0.8175	pathogenic	-0.03	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
C/F	0.2115	likely_benign	0.2415	benign	-1.223	Destabilizing	1.0	D	0.854	deleterious	N	0.49650491	None	None	N
C/G	0.2771	likely_benign	0.3291	benign	-2.2	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.593103063	None	None	N
C/H	0.4432	ambiguous	0.5025	ambiguous	-2.082	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
C/I	0.3671	ambiguous	0.3923	ambiguous	-1.038	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
C/K	0.6726	likely_pathogenic	0.7331	pathogenic	-0.848	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
C/L	0.4018	ambiguous	0.4281	ambiguous	-1.038	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
C/M	0.6123	likely_pathogenic	0.6282	pathogenic	-0.039	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
C/N	0.5065	ambiguous	0.5685	pathogenic	-0.939	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
C/P	0.7878	likely_pathogenic	0.8605	pathogenic	-1.293	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
C/Q	0.5681	likely_pathogenic	0.6319	pathogenic	-0.763	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
C/R	0.3415	ambiguous	0.3992	ambiguous	-0.793	Destabilizing	1.0	D	0.862	deleterious	N	0.508971841	None	None	N
C/S	0.3889	ambiguous	0.4635	ambiguous	-1.526	Destabilizing	1.0	D	0.782	deleterious	N	0.508547372	None	None	N
C/T	0.5054	ambiguous	0.5633	ambiguous	-1.201	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
C/V	0.389	ambiguous	0.4204	ambiguous	-1.293	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
C/W	0.4938	ambiguous	0.5324	ambiguous	-1.185	Destabilizing	1.0	D	0.853	deleterious	D	0.593243597	None	None	N
C/Y	0.2242	likely_benign	0.2536	benign	-1.187	Destabilizing	1.0	D	0.855	deleterious	N	0.498258421	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.