TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16119	48580;48581;48582	chr2:178615746;178615745;178615744	chr2:179480473;179480472;179480471
N2AB	14478	43657;43658;43659	chr2:178615746;178615745;178615744	chr2:179480473;179480472;179480471
N2A	13551	40876;40877;40878	chr2:178615746;178615745;178615744	chr2:179480473;179480472;179480471
N2B	7054	21385;21386;21387	chr2:178615746;178615745;178615744	chr2:179480473;179480472;179480471
Novex-1	7179	21760;21761;21762	chr2:178615746;178615745;178615744	chr2:179480473;179480472;179480471
Novex-2	7246	21961;21962;21963	chr2:178615746;178615745;178615744	chr2:179480473;179480472;179480471
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-4
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.0973
• 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/I	rs1576477522	None	0.9	D	0.714	0.573	0.807069209449	gnomAD-4.0.0	1.595E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86546E-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	0.8164	likely_pathogenic	0.8794	pathogenic	-2.632	Highly Destabilizing	0.983	D	0.776	deleterious	None	None	None	None	N
L/C	0.8096	likely_pathogenic	0.8602	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/D	0.9984	likely_pathogenic	0.9989	pathogenic	-3.271	Highly Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
L/E	0.9916	likely_pathogenic	0.9948	pathogenic	-3.048	Highly Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
L/F	0.7456	likely_pathogenic	0.8258	pathogenic	-1.693	Destabilizing	0.997	D	0.801	deleterious	D	0.814334827	None	None	N
L/G	0.9718	likely_pathogenic	0.9815	pathogenic	-3.185	Highly Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
L/H	0.9764	likely_pathogenic	0.9866	pathogenic	-2.753	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.813066532	None	None	N
L/I	0.1988	likely_benign	0.2471	benign	-1.028	Destabilizing	0.9	D	0.714	prob.delet.	D	0.719692842	None	None	N
L/K	0.9874	likely_pathogenic	0.9914	pathogenic	-2.154	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
L/M	0.2809	likely_benign	0.3466	ambiguous	-0.972	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
L/N	0.9835	likely_pathogenic	0.989	pathogenic	-2.535	Highly Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
L/P	0.9849	likely_pathogenic	0.9904	pathogenic	-1.544	Destabilizing	0.999	D	0.881	deleterious	D	0.813066532	None	None	N
L/Q	0.9582	likely_pathogenic	0.9759	pathogenic	-2.405	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
L/R	0.9688	likely_pathogenic	0.9794	pathogenic	-1.834	Destabilizing	0.999	D	0.857	deleterious	D	0.761063254	None	None	N
L/S	0.968	likely_pathogenic	0.9813	pathogenic	-3.185	Highly Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
L/T	0.8007	likely_pathogenic	0.8703	pathogenic	-2.812	Highly Destabilizing	0.983	D	0.818	deleterious	None	None	None	None	N
L/V	0.1784	likely_benign	0.2402	benign	-1.544	Destabilizing	0.198	N	0.455	neutral	D	0.557923477	None	None	N
L/W	0.9755	likely_pathogenic	0.9856	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/Y	0.9755	likely_pathogenic	0.985	pathogenic	-1.857	Destabilizing	0.999	D	0.812	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.