TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8406	25441;25442;25443	chr2:178717658;178717657;178717656	chr2:179582385;179582384;179582383
N2AB	8089	24490;24491;24492	chr2:178717658;178717657;178717656	chr2:179582385;179582384;179582383
N2A	7162	21709;21710;21711	chr2:178717658;178717657;178717656	chr2:179582385;179582384;179582383
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-69
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1637
• 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/M	rs1183682062	-1.009	0.01	N	0.237	0.091	0.302793454619	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
L/M	rs1183682062	-1.009	0.01	N	0.237	0.091	0.302793454619	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85959E-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	0.3971	ambiguous	0.3869	ambiguous	-2.592	Highly Destabilizing	0.644	D	0.553	neutral	None	None	None	None	N
L/C	0.4821	ambiguous	0.5017	ambiguous	-2.013	Highly Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
L/D	0.8743	likely_pathogenic	0.8799	pathogenic	-2.917	Highly Destabilizing	0.984	D	0.691	prob.neutral	None	None	None	None	N
L/E	0.5445	ambiguous	0.5599	ambiguous	-2.811	Highly Destabilizing	0.979	D	0.699	prob.neutral	None	None	None	None	N
L/F	0.1444	likely_benign	0.1363	benign	-1.81	Destabilizing	0.008	N	0.359	neutral	N	0.394838381	None	None	N
L/G	0.7201	likely_pathogenic	0.7227	pathogenic	-3.048	Highly Destabilizing	0.947	D	0.701	prob.neutral	None	None	None	None	N
L/H	0.2728	likely_benign	0.2848	benign	-2.379	Highly Destabilizing	0.997	D	0.656	neutral	None	None	None	None	N
L/I	0.0717	likely_benign	0.068	benign	-1.32	Destabilizing	None	N	0.142	neutral	None	None	None	None	N
L/K	0.3765	ambiguous	0.3894	ambiguous	-2.054	Highly Destabilizing	0.474	N	0.667	neutral	None	None	None	None	N
L/M	0.1059	likely_benign	0.0985	benign	-1.114	Destabilizing	0.01	N	0.237	neutral	N	0.431319256	None	None	N
L/N	0.56	ambiguous	0.5508	ambiguous	-2.137	Highly Destabilizing	0.984	D	0.701	prob.neutral	None	None	None	None	N
L/P	0.9423	likely_pathogenic	0.9436	pathogenic	-1.721	Destabilizing	0.995	D	0.698	prob.neutral	None	None	None	None	N
L/Q	0.2208	likely_benign	0.232	benign	-2.21	Highly Destabilizing	0.927	D	0.668	neutral	None	None	None	None	N
L/R	0.2492	likely_benign	0.2761	benign	-1.486	Destabilizing	0.924	D	0.657	neutral	None	None	None	None	N
L/S	0.412	ambiguous	0.4061	ambiguous	-2.78	Highly Destabilizing	0.868	D	0.623	neutral	N	0.472704519	None	None	N
L/T	0.2259	likely_benign	0.2184	benign	-2.544	Highly Destabilizing	0.724	D	0.6	neutral	None	None	None	None	N
L/V	0.0766	likely_benign	0.0772	benign	-1.721	Destabilizing	None	N	0.154	neutral	N	0.388045695	None	None	N
L/W	0.276	likely_benign	0.2819	benign	-2.083	Highly Destabilizing	0.999	D	0.61	neutral	N	0.519458316	None	None	N
L/Y	0.3622	ambiguous	0.3693	ambiguous	-1.87	Destabilizing	0.417	N	0.687	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.