TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13741	41446;41447;41448	chr2:178636506;178636505;178636504	chr2:179501233;179501232;179501231
N2AB	12100	36523;36524;36525	chr2:178636506;178636505;178636504	chr2:179501233;179501232;179501231
N2A	11173	33742;33743;33744	chr2:178636506;178636505;178636504	chr2:179501233;179501232;179501231
N2B	4676	14251;14252;14253	chr2:178636506;178636505;178636504	chr2:179501233;179501232;179501231
Novex-1	4801	14626;14627;14628	chr2:178636506;178636505;178636504	chr2:179501233;179501232;179501231
Novex-2	4868	14827;14828;14829	chr2:178636506;178636505;178636504	chr2:179501233;179501232;179501231
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: Ig-87
• Domain position: 58
• Structural Position: 136
• Q(SASA): 0.0972
• 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/G	None	None	0.805	N	0.753	0.218	0.317667799068	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85958E-06	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
R/A	0.9923	likely_pathogenic	0.9931	pathogenic	-1.366	Destabilizing	0.693	D	0.731	prob.delet.	None	None	None	None	N
R/C	0.8778	likely_pathogenic	0.8826	pathogenic	-1.702	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
R/D	0.9985	likely_pathogenic	0.9986	pathogenic	-1.084	Destabilizing	0.975	D	0.769	deleterious	None	None	None	None	N
R/E	0.9834	likely_pathogenic	0.9841	pathogenic	-0.926	Destabilizing	0.916	D	0.696	prob.neutral	None	None	None	None	N
R/F	0.9937	likely_pathogenic	0.9952	pathogenic	-1.079	Destabilizing	0.987	D	0.844	deleterious	None	None	None	None	N
R/G	0.9852	likely_pathogenic	0.9875	pathogenic	-1.673	Destabilizing	0.805	D	0.753	deleterious	N	0.437751681	None	None	N
R/H	0.7963	likely_pathogenic	0.828	pathogenic	-1.592	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
R/I	0.9828	likely_pathogenic	0.9812	pathogenic	-0.514	Destabilizing	0.983	D	0.849	deleterious	N	0.49479484	None	None	N
R/K	0.818	likely_pathogenic	0.8345	pathogenic	-1.411	Destabilizing	0.773	D	0.664	neutral	N	0.437417152	None	None	N
R/L	0.9685	likely_pathogenic	0.9701	pathogenic	-0.514	Destabilizing	0.916	D	0.768	deleterious	None	None	None	None	N
R/M	0.9885	likely_pathogenic	0.9889	pathogenic	-0.903	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
R/N	0.9949	likely_pathogenic	0.9955	pathogenic	-1.268	Destabilizing	0.916	D	0.719	prob.delet.	None	None	None	None	N
R/P	0.9992	likely_pathogenic	0.9991	pathogenic	-0.782	Destabilizing	0.987	D	0.809	deleterious	None	None	None	None	N
R/Q	0.7798	likely_pathogenic	0.8111	pathogenic	-1.264	Destabilizing	0.975	D	0.731	prob.delet.	None	None	None	None	N
R/S	0.9947	likely_pathogenic	0.9953	pathogenic	-1.965	Destabilizing	0.099	N	0.548	neutral	N	0.44219268	None	None	N
R/T	0.9899	likely_pathogenic	0.9898	pathogenic	-1.619	Destabilizing	0.805	D	0.765	deleterious	N	0.427418971	None	None	N
R/V	0.9826	likely_pathogenic	0.9819	pathogenic	-0.782	Destabilizing	0.975	D	0.821	deleterious	None	None	None	None	N
R/W	0.9157	likely_pathogenic	0.9202	pathogenic	-0.774	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
R/Y	0.9718	likely_pathogenic	0.9795	pathogenic	-0.442	Destabilizing	0.996	D	0.799	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.