TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26086	78481;78482;78483	chr2:178567876;178567875;178567874	chr2:179432603;179432602;179432601
N2AB	24445	73558;73559;73560	chr2:178567876;178567875;178567874	chr2:179432603;179432602;179432601
N2A	23518	70777;70778;70779	chr2:178567876;178567875;178567874	chr2:179432603;179432602;179432601
N2B	17021	51286;51287;51288	chr2:178567876;178567875;178567874	chr2:179432603;179432602;179432601
Novex-1	17146	51661;51662;51663	chr2:178567876;178567875;178567874	chr2:179432603;179432602;179432601
Novex-2	17213	51862;51863;51864	chr2:178567876;178567875;178567874	chr2:179432603;179432602;179432601
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-77
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.5439
• 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
R/K	rs1394737177	-0.124	0.894	N	0.497	0.111	0.250039746154	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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
R/A	0.7179	likely_pathogenic	0.6465	pathogenic	-0.634	Destabilizing	0.982	D	0.533	neutral	None	None	None	None	N
R/C	0.215	likely_benign	0.1705	benign	-0.583	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
R/D	0.9491	likely_pathogenic	0.9292	pathogenic	-0.076	Destabilizing	0.995	D	0.56	neutral	None	None	None	None	N
R/E	0.7036	likely_pathogenic	0.6412	pathogenic	0.012	Stabilizing	0.965	D	0.483	neutral	None	None	None	None	N
R/F	0.7252	likely_pathogenic	0.6762	pathogenic	-0.698	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
R/G	0.6593	likely_pathogenic	0.5892	pathogenic	-0.893	Destabilizing	0.988	D	0.499	neutral	N	0.462487106	None	None	N
R/H	0.1507	likely_benign	0.121	benign	-1.233	Destabilizing	0.997	D	0.537	neutral	None	None	None	None	N
R/I	0.4097	ambiguous	0.3927	ambiguous	0.043	Stabilizing	0.999	D	0.845	deleterious	N	0.467375404	None	None	N
R/K	0.1605	likely_benign	0.1362	benign	-0.661	Destabilizing	0.894	D	0.497	neutral	N	0.475050525	None	None	N
R/L	0.398	ambiguous	0.3569	ambiguous	0.043	Stabilizing	0.982	D	0.499	neutral	None	None	None	None	N
R/M	0.4775	ambiguous	0.4391	ambiguous	-0.189	Destabilizing	1.0	D	0.552	neutral	None	None	None	None	N
R/N	0.8543	likely_pathogenic	0.8056	pathogenic	-0.113	Destabilizing	0.997	D	0.558	neutral	None	None	None	None	N
R/P	0.9857	likely_pathogenic	0.9827	pathogenic	-0.162	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
R/Q	0.1542	likely_benign	0.1342	benign	-0.349	Destabilizing	0.831	D	0.307	neutral	None	None	None	None	N
R/S	0.8021	likely_pathogenic	0.7448	pathogenic	-0.809	Destabilizing	0.976	D	0.609	neutral	N	0.460601001	None	None	N
R/T	0.5578	ambiguous	0.4952	ambiguous	-0.563	Destabilizing	0.997	D	0.526	neutral	N	0.489834526	None	None	N
R/V	0.4986	ambiguous	0.4643	ambiguous	-0.162	Destabilizing	0.997	D	0.826	deleterious	None	None	None	None	N
R/W	0.2907	likely_benign	0.2751	benign	-0.454	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
R/Y	0.5551	ambiguous	0.4964	ambiguous	-0.119	Destabilizing	0.999	D	0.832	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.