TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22458	67597;67598;67599	chr2:178579825;178579824;178579823	chr2:179444552;179444551;179444550
N2AB	20817	62674;62675;62676	chr2:178579825;178579824;178579823	chr2:179444552;179444551;179444550
N2A	19890	59893;59894;59895	chr2:178579825;178579824;178579823	chr2:179444552;179444551;179444550
N2B	13393	40402;40403;40404	chr2:178579825;178579824;178579823	chr2:179444552;179444551;179444550
Novex-1	13518	40777;40778;40779	chr2:178579825;178579824;178579823	chr2:179444552;179444551;179444550
Novex-2	13585	40978;40979;40980	chr2:178579825;178579824;178579823	chr2:179444552;179444551;179444550
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-51
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1554
• 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/P	None	None	0.999	N	0.843	0.614	0.772403177195	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86038E-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	0.8529	likely_pathogenic	0.8256	pathogenic	-2.12	Highly Destabilizing	0.992	D	0.717	prob.delet.	None	None	None	None	N
L/C	0.777	likely_pathogenic	0.7542	pathogenic	-1.395	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
L/D	0.9959	likely_pathogenic	0.9944	pathogenic	-1.862	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
L/E	0.9818	likely_pathogenic	0.974	pathogenic	-1.721	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
L/F	0.4368	ambiguous	0.4541	ambiguous	-1.29	Destabilizing	0.154	N	0.413	neutral	None	None	None	None	N
L/G	0.9605	likely_pathogenic	0.9478	pathogenic	-2.591	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
L/H	0.9549	likely_pathogenic	0.9423	pathogenic	-1.919	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/I	0.1651	likely_benign	0.1613	benign	-0.819	Destabilizing	0.983	D	0.697	prob.neutral	None	None	None	None	N
L/K	0.9545	likely_pathogenic	0.9376	pathogenic	-1.581	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
L/M	0.2564	likely_benign	0.2377	benign	-0.697	Destabilizing	0.999	D	0.733	prob.delet.	N	0.496084356	None	None	N
L/N	0.9729	likely_pathogenic	0.9637	pathogenic	-1.677	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
L/P	0.9264	likely_pathogenic	0.9016	pathogenic	-1.227	Destabilizing	0.999	D	0.843	deleterious	N	0.47816348	None	None	N
L/Q	0.9265	likely_pathogenic	0.9009	pathogenic	-1.657	Destabilizing	0.999	D	0.811	deleterious	N	0.51207547	None	None	N
L/R	0.9325	likely_pathogenic	0.907	pathogenic	-1.183	Destabilizing	0.999	D	0.813	deleterious	D	0.52359636	None	None	N
L/S	0.9652	likely_pathogenic	0.9545	pathogenic	-2.383	Highly Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
L/T	0.8152	likely_pathogenic	0.7735	pathogenic	-2.103	Highly Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
L/V	0.1666	likely_benign	0.158	benign	-1.227	Destabilizing	0.978	D	0.728	prob.delet.	N	0.478755339	None	None	N
L/W	0.8587	likely_pathogenic	0.8388	pathogenic	-1.552	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/Y	0.9075	likely_pathogenic	0.8959	pathogenic	-1.262	Destabilizing	0.99	D	0.787	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.