TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14909	44950;44951;44952	chr2:178624555;178624554;178624553	chr2:179489282;179489281;179489280
N2AB	13268	40027;40028;40029	chr2:178624555;178624554;178624553	chr2:179489282;179489281;179489280
N2A	12341	37246;37247;37248	chr2:178624555;178624554;178624553	chr2:179489282;179489281;179489280
N2B	5844	17755;17756;17757	chr2:178624555;178624554;178624553	chr2:179489282;179489281;179489280
Novex-1	5969	18130;18131;18132	chr2:178624555;178624554;178624553	chr2:179489282;179489281;179489280
Novex-2	6036	18331;18332;18333	chr2:178624555;178624554;178624553	chr2:179489282;179489281;179489280
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: Ig-100
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0555
• 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/F	None	None	1.0	D	0.817	0.608	0.55810899713	gnomAD-4.0.0	1.5934E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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	0.9437	likely_pathogenic	0.9617	pathogenic	-2.481	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
L/C	0.9446	likely_pathogenic	0.971	pathogenic	-1.525	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9997	pathogenic	-3.227	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/E	0.9961	likely_pathogenic	0.9977	pathogenic	-2.927	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/F	0.7011	likely_pathogenic	0.8157	pathogenic	-1.579	Destabilizing	1.0	D	0.817	deleterious	D	0.606504859	None	None	N
L/G	0.9898	likely_pathogenic	0.9945	pathogenic	-3.013	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/H	0.9894	likely_pathogenic	0.9944	pathogenic	-2.863	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.677697762	None	None	N
L/I	0.386	ambiguous	0.4512	ambiguous	-0.856	Destabilizing	0.999	D	0.627	neutral	D	0.525127171	None	None	N
L/K	0.9904	likely_pathogenic	0.9949	pathogenic	-2.021	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/M	0.4429	ambiguous	0.5101	ambiguous	-1.017	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
L/N	0.9965	likely_pathogenic	0.9979	pathogenic	-2.812	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/P	0.9978	likely_pathogenic	0.9988	pathogenic	-1.393	Destabilizing	1.0	D	0.899	deleterious	D	0.677697762	None	None	N
L/Q	0.9883	likely_pathogenic	0.9933	pathogenic	-2.395	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/R	0.9788	likely_pathogenic	0.9885	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.9	deleterious	D	0.677697762	None	None	N
L/S	0.9967	likely_pathogenic	0.9983	pathogenic	-3.158	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/T	0.9814	likely_pathogenic	0.9892	pathogenic	-2.704	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/V	0.4865	ambiguous	0.5963	pathogenic	-1.393	Destabilizing	0.999	D	0.622	neutral	D	0.545851644	None	None	N
L/W	0.9618	likely_pathogenic	0.9832	pathogenic	-1.866	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/Y	0.9636	likely_pathogenic	0.9806	pathogenic	-1.752	Destabilizing	1.0	D	0.866	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.