TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24945	75058;75059;75060	chr2:178571299;178571298;178571297	chr2:179436026;179436025;179436024
N2AB	23304	70135;70136;70137	chr2:178571299;178571298;178571297	chr2:179436026;179436025;179436024
N2A	22377	67354;67355;67356	chr2:178571299;178571298;178571297	chr2:179436026;179436025;179436024
N2B	15880	47863;47864;47865	chr2:178571299;178571298;178571297	chr2:179436026;179436025;179436024
Novex-1	16005	48238;48239;48240	chr2:178571299;178571298;178571297	chr2:179436026;179436025;179436024
Novex-2	16072	48439;48440;48441	chr2:178571299;178571298;178571297	chr2:179436026;179436025;179436024
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-69
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0738
• 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/V	None	None	0.025	N	0.335	0.028	0.101711395817	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	3.66354E-05

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	0.8305	likely_pathogenic	0.8666	pathogenic	-3.207	Highly Destabilizing	0.845	D	0.577	neutral	None	None	None	None	N
L/C	0.8233	likely_pathogenic	0.8436	pathogenic	-2.071	Highly Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-3.611	Highly Destabilizing	0.996	D	0.842	deleterious	None	None	None	None	N
L/E	0.9961	likely_pathogenic	0.9965	pathogenic	-3.301	Highly Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
L/F	0.816	likely_pathogenic	0.8515	pathogenic	-1.877	Destabilizing	0.975	D	0.651	neutral	None	None	None	None	N
L/G	0.9872	likely_pathogenic	0.9898	pathogenic	-3.759	Highly Destabilizing	0.987	D	0.84	deleterious	None	None	None	None	N
L/H	0.993	likely_pathogenic	0.9939	pathogenic	-3.234	Highly Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
L/I	0.099	likely_benign	0.11	benign	-1.504	Destabilizing	0.099	N	0.293	neutral	N	0.421986831	None	None	N
L/K	0.9949	likely_pathogenic	0.9948	pathogenic	-2.469	Highly Destabilizing	0.987	D	0.808	deleterious	None	None	None	None	N
L/M	0.311	likely_benign	0.3243	benign	-1.662	Destabilizing	0.987	D	0.602	neutral	None	None	None	None	N
L/N	0.9973	likely_pathogenic	0.9976	pathogenic	-3.202	Highly Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
L/P	0.9952	likely_pathogenic	0.9961	pathogenic	-2.07	Highly Destabilizing	0.994	D	0.847	deleterious	D	0.526511832	None	None	N
L/Q	0.9866	likely_pathogenic	0.9876	pathogenic	-2.842	Highly Destabilizing	0.994	D	0.832	deleterious	D	0.526511832	None	None	N
L/R	0.9889	likely_pathogenic	0.9892	pathogenic	-2.487	Highly Destabilizing	0.983	D	0.828	deleterious	D	0.526511832	None	None	N
L/S	0.9864	likely_pathogenic	0.9894	pathogenic	-3.645	Highly Destabilizing	0.987	D	0.797	deleterious	None	None	None	None	N
L/T	0.8783	likely_pathogenic	0.8926	pathogenic	-3.188	Highly Destabilizing	0.975	D	0.649	neutral	None	None	None	None	N
L/V	0.0939	likely_benign	0.0998	benign	-2.07	Highly Destabilizing	0.025	N	0.335	neutral	N	0.411110902	None	None	N
L/W	0.9849	likely_pathogenic	0.9879	pathogenic	-2.076	Highly Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
L/Y	0.9867	likely_pathogenic	0.9888	pathogenic	-2.09	Highly Destabilizing	0.987	D	0.689	prob.neutral	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.