TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6574	19945;19946;19947	chr2:178727858;178727857;178727856	chr2:179592585;179592584;179592583
N2AB	6257	18994;18995;18996	chr2:178727858;178727857;178727856	chr2:179592585;179592584;179592583
N2A	5330	16213;16214;16215	chr2:178727858;178727857;178727856	chr2:179592585;179592584;179592583
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-50
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1177
• 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
P/Q	None	None	1.0	D	0.892	0.653	0.83602636732	gnomAD-4.0.0	1.67444E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.97115E-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
P/A	0.3658	ambiguous	0.4189	ambiguous	-1.805	Destabilizing	0.995	D	0.815	deleterious	D	0.628156733	None	None	N
P/C	0.9482	likely_pathogenic	0.9696	pathogenic	-1.663	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/D	0.9966	likely_pathogenic	0.9982	pathogenic	-1.487	Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
P/E	0.9884	likely_pathogenic	0.9937	pathogenic	-1.384	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
P/F	0.993	likely_pathogenic	0.9965	pathogenic	-1.266	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/G	0.9416	likely_pathogenic	0.9626	pathogenic	-2.227	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
P/H	0.9853	likely_pathogenic	0.9928	pathogenic	-1.748	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/I	0.9054	likely_pathogenic	0.9517	pathogenic	-0.695	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/K	0.9922	likely_pathogenic	0.9959	pathogenic	-1.307	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/L	0.7854	likely_pathogenic	0.8738	pathogenic	-0.695	Destabilizing	1.0	D	0.894	deleterious	D	0.628560341	None	None	N
P/M	0.9656	likely_pathogenic	0.9823	pathogenic	-0.829	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
P/N	0.9939	likely_pathogenic	0.997	pathogenic	-1.315	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/Q	0.9746	likely_pathogenic	0.9873	pathogenic	-1.345	Destabilizing	1.0	D	0.892	deleterious	D	0.628762145	None	None	N
P/R	0.9728	likely_pathogenic	0.9855	pathogenic	-1.015	Destabilizing	1.0	D	0.905	deleterious	D	0.628762145	None	None	N
P/S	0.8779	likely_pathogenic	0.9241	pathogenic	-2.039	Highly Destabilizing	0.992	D	0.731	prob.delet.	D	0.628358537	None	None	N
P/T	0.8511	likely_pathogenic	0.9148	pathogenic	-1.799	Destabilizing	0.999	D	0.871	deleterious	D	0.628560341	None	None	N
P/V	0.7691	likely_pathogenic	0.8581	pathogenic	-1.033	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/W	0.9985	likely_pathogenic	0.9993	pathogenic	-1.491	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/Y	0.9956	likely_pathogenic	0.9977	pathogenic	-1.16	Destabilizing	1.0	D	0.911	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.