TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22222	66889;66890;66891	chr2:178581604;178581603;178581602	chr2:179446331;179446330;179446329
N2AB	20581	61966;61967;61968	chr2:178581604;178581603;178581602	chr2:179446331;179446330;179446329
N2A	19654	59185;59186;59187	chr2:178581604;178581603;178581602	chr2:179446331;179446330;179446329
N2B	13157	39694;39695;39696	chr2:178581604;178581603;178581602	chr2:179446331;179446330;179446329
Novex-1	13282	40069;40070;40071	chr2:178581604;178581603;178581602	chr2:179446331;179446330;179446329
Novex-2	13349	40270;40271;40272	chr2:178581604;178581603;178581602	chr2:179446331;179446330;179446329
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-49
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.123
• 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
L/M	None	None	1.0	D	0.835	0.626	0.818363800835	gnomAD-4.0.0	1.36929E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79977E-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
L/A	0.9753	likely_pathogenic	0.9753	pathogenic	-2.469	Highly Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
L/C	0.9515	likely_pathogenic	0.9557	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9992	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/E	0.9961	likely_pathogenic	0.996	pathogenic	-1.903	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/F	0.8909	likely_pathogenic	0.8959	pathogenic	-1.684	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/G	0.9929	likely_pathogenic	0.9926	pathogenic	-2.965	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/H	0.9934	likely_pathogenic	0.9935	pathogenic	-2.198	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/I	0.4854	ambiguous	0.4941	ambiguous	-1.073	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
L/K	0.9895	likely_pathogenic	0.9901	pathogenic	-1.713	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/M	0.5886	likely_pathogenic	0.5894	pathogenic	-1.077	Destabilizing	1.0	D	0.835	deleterious	D	0.602756115	None	None	N
L/N	0.9946	likely_pathogenic	0.9946	pathogenic	-1.879	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/P	0.9958	likely_pathogenic	0.9955	pathogenic	-1.514	Destabilizing	1.0	D	0.843	deleterious	D	0.674141386	None	None	N
L/Q	0.9871	likely_pathogenic	0.9875	pathogenic	-1.856	Destabilizing	1.0	D	0.849	deleterious	D	0.648603274	None	None	N
L/R	0.9838	likely_pathogenic	0.9845	pathogenic	-1.31	Destabilizing	1.0	D	0.84	deleterious	D	0.658122025	None	None	N
L/S	0.9968	likely_pathogenic	0.9968	pathogenic	-2.708	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/T	0.9819	likely_pathogenic	0.9819	pathogenic	-2.393	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/V	0.6207	likely_pathogenic	0.6266	pathogenic	-1.514	Destabilizing	0.999	D	0.825	deleterious	D	0.595821536	None	None	N
L/W	0.9892	likely_pathogenic	0.9907	pathogenic	-1.853	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/Y	0.9886	likely_pathogenic	0.99	pathogenic	-1.602	Destabilizing	1.0	D	0.822	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.