TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3373	10342;10343;10344	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895
N2AB	3373	10342;10343;10344	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895
N2A	3373	10342;10343;10344	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895
N2B	3327	10204;10205;10206	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895
Novex-1	3327	10204;10205;10206	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895
Novex-2	3327	10204;10205;10206	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895
Novex-3	3373	10342;10343;10344	chr2:178759170;178759169;178759168	chr2:179623897;179623896;179623895

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-24
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.4697
• Predicted PPI site: I

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/P	None	None	1.0	N	0.744	0.627	0.798287381842	gnomAD-4.0.0	1.36831E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79872E-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	0.7423	likely_pathogenic	0.7439	pathogenic	-2.034	Highly Destabilizing	0.997	D	0.49	neutral	None	None	None	None	I
L/C	0.8732	likely_pathogenic	0.8453	pathogenic	-1.466	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
L/D	0.984	likely_pathogenic	0.9828	pathogenic	-1.341	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
L/E	0.9096	likely_pathogenic	0.8908	pathogenic	-1.288	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
L/F	0.5193	ambiguous	0.5408	ambiguous	-1.442	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
L/G	0.9313	likely_pathogenic	0.9271	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
L/H	0.8825	likely_pathogenic	0.8548	pathogenic	-1.644	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
L/I	0.1471	likely_benign	0.1416	benign	-1.009	Destabilizing	0.981	D	0.497	neutral	N	0.516666753	None	None	I
L/K	0.8683	likely_pathogenic	0.8352	pathogenic	-1.33	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
L/M	0.2077	likely_benign	0.1873	benign	-0.887	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
L/N	0.9116	likely_pathogenic	0.8998	pathogenic	-1.209	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
L/P	0.6785	likely_pathogenic	0.7303	pathogenic	-1.321	Destabilizing	1.0	D	0.744	deleterious	N	0.383085287	None	None	I
L/Q	0.738	likely_pathogenic	0.6733	pathogenic	-1.334	Destabilizing	1.0	D	0.693	prob.neutral	D	0.558899366	None	None	I
L/R	0.8102	likely_pathogenic	0.7745	pathogenic	-0.821	Destabilizing	1.0	D	0.703	prob.neutral	N	0.514231533	None	None	I
L/S	0.8813	likely_pathogenic	0.8547	pathogenic	-1.947	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
L/T	0.6645	likely_pathogenic	0.6379	pathogenic	-1.76	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
L/V	0.1736	likely_benign	0.1561	benign	-1.321	Destabilizing	0.767	D	0.187	neutral	N	0.496806453	None	None	I
L/W	0.8165	likely_pathogenic	0.8044	pathogenic	-1.512	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
L/Y	0.9067	likely_pathogenic	0.8939	pathogenic	-1.285	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I

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.