TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24280	73063;73064;73065	chr2:178573294;178573293;178573292	chr2:179438021;179438020;179438019
N2AB	22639	68140;68141;68142	chr2:178573294;178573293;178573292	chr2:179438021;179438020;179438019
N2A	21712	65359;65360;65361	chr2:178573294;178573293;178573292	chr2:179438021;179438020;179438019
N2B	15215	45868;45869;45870	chr2:178573294;178573293;178573292	chr2:179438021;179438020;179438019
Novex-1	15340	46243;46244;46245	chr2:178573294;178573293;178573292	chr2:179438021;179438020;179438019
Novex-2	15407	46444;46445;46446	chr2:178573294;178573293;178573292	chr2:179438021;179438020;179438019
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-64
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.1423
• 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	N	0.681	0.263	0.464183351471	gnomAD-4.0.0	1.65939E-06	None	None	None	None	N	None	0	0	None	0	2.79799E-05	None	0	0	0	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	0.4842	ambiguous	0.4751	ambiguous	-2.123	Highly Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
L/C	0.5351	ambiguous	0.5524	ambiguous	-1.121	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/D	0.8529	likely_pathogenic	0.8756	pathogenic	-2.45	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/E	0.582	likely_pathogenic	0.586	pathogenic	-2.299	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/F	0.3501	ambiguous	0.3452	ambiguous	-1.423	Destabilizing	1.0	D	0.681	prob.neutral	N	0.475101313	None	None	N
L/G	0.6676	likely_pathogenic	0.6953	pathogenic	-2.549	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/H	0.4306	ambiguous	0.4372	ambiguous	-1.829	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/I	0.1648	likely_benign	0.156	benign	-0.927	Destabilizing	0.999	D	0.535	neutral	N	0.471391557	None	None	N
L/K	0.3383	likely_benign	0.3445	ambiguous	-1.592	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/M	0.1486	likely_benign	0.148	benign	-0.65	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
L/N	0.4572	ambiguous	0.5187	ambiguous	-1.774	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/P	0.5677	likely_pathogenic	0.5688	pathogenic	-1.305	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/Q	0.2399	likely_benign	0.2426	benign	-1.795	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/R	0.2463	likely_benign	0.2433	benign	-1.127	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/S	0.5084	ambiguous	0.5185	ambiguous	-2.329	Highly Destabilizing	1.0	D	0.709	prob.delet.	N	0.474594334	None	None	N
L/T	0.2111	likely_benign	0.2171	benign	-2.055	Highly Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
L/V	0.1331	likely_benign	0.131	benign	-1.305	Destabilizing	0.999	D	0.574	neutral	N	0.478620032	None	None	N
L/W	0.553	ambiguous	0.5524	ambiguous	-1.736	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/Y	0.6143	likely_pathogenic	0.6176	pathogenic	-1.408	Destabilizing	1.0	D	0.739	prob.delet.	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.