TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17407	52444;52445;52446	chr2:178608792;178608791;178608790	chr2:179473519;179473518;179473517
N2AB	15766	47521;47522;47523	chr2:178608792;178608791;178608790	chr2:179473519;179473518;179473517
N2A	14839	44740;44741;44742	chr2:178608792;178608791;178608790	chr2:179473519;179473518;179473517
N2B	8342	25249;25250;25251	chr2:178608792;178608791;178608790	chr2:179473519;179473518;179473517
Novex-1	8467	25624;25625;25626	chr2:178608792;178608791;178608790	chr2:179473519;179473518;179473517
Novex-2	8534	25825;25826;25827	chr2:178608792;178608791;178608790	chr2:179473519;179473518;179473517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-14
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0957
• 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
E/G	None	None	1.0	D	0.803	0.473	0.567170738818	gnomAD-4.0.0	1.59376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8619E-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
E/A	0.9177	likely_pathogenic	0.9007	pathogenic	-1.976	Destabilizing	0.999	D	0.727	prob.delet.	D	0.522683036	None	None	N
E/C	0.979	likely_pathogenic	0.9803	pathogenic	-0.928	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/D	0.8452	likely_pathogenic	0.852	pathogenic	-1.964	Destabilizing	0.999	D	0.651	neutral	N	0.482942581	None	None	N
E/F	0.9902	likely_pathogenic	0.9903	pathogenic	-1.676	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
E/G	0.9516	likely_pathogenic	0.9393	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.803	deleterious	D	0.531205413	None	None	N
E/H	0.9706	likely_pathogenic	0.9693	pathogenic	-1.365	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/I	0.9663	likely_pathogenic	0.9641	pathogenic	-0.917	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/K	0.9556	likely_pathogenic	0.9511	pathogenic	-1.676	Destabilizing	0.999	D	0.647	neutral	N	0.516642649	None	None	N
E/L	0.9423	likely_pathogenic	0.9428	pathogenic	-0.917	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/M	0.9514	likely_pathogenic	0.945	pathogenic	-0.159	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/N	0.9862	likely_pathogenic	0.985	pathogenic	-1.859	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9998	pathogenic	-1.259	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Q	0.5778	likely_pathogenic	0.5536	ambiguous	-1.601	Destabilizing	1.0	D	0.728	prob.delet.	N	0.465772924	None	None	N
E/R	0.9619	likely_pathogenic	0.9598	pathogenic	-1.448	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/S	0.9448	likely_pathogenic	0.936	pathogenic	-2.504	Highly Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
E/T	0.9678	likely_pathogenic	0.9636	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/V	0.9198	likely_pathogenic	0.915	pathogenic	-1.259	Destabilizing	1.0	D	0.817	deleterious	D	0.523443505	None	None	N
E/W	0.9926	likely_pathogenic	0.9934	pathogenic	-1.702	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/Y	0.983	likely_pathogenic	0.983	pathogenic	-1.468	Destabilizing	1.0	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.