TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17599	53020;53021;53022	chr2:178607992;178607991;178607990	chr2:179472719;179472718;179472717
N2AB	15958	48097;48098;48099	chr2:178607992;178607991;178607990	chr2:179472719;179472718;179472717
N2A	15031	45316;45317;45318	chr2:178607992;178607991;178607990	chr2:179472719;179472718;179472717
N2B	8534	25825;25826;25827	chr2:178607992;178607991;178607990	chr2:179472719;179472718;179472717
Novex-1	8659	26200;26201;26202	chr2:178607992;178607991;178607990	chr2:179472719;179472718;179472717
Novex-2	8726	26401;26402;26403	chr2:178607992;178607991;178607990	chr2:179472719;179472718;179472717
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-16
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2887
• 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
G/E	None	None	0.709	N	0.818	0.355	0.412458657427	gnomAD-4.0.0	1.59294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8611E-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
G/A	0.1488	likely_benign	0.1418	benign	-0.461	Destabilizing	0.018	N	0.48	neutral	N	0.442255821	None	None	I
G/C	0.2875	likely_benign	0.2822	benign	-0.896	Destabilizing	0.98	D	0.799	deleterious	None	None	None	None	I
G/D	0.5408	ambiguous	0.5317	ambiguous	-0.816	Destabilizing	0.764	D	0.794	deleterious	None	None	None	None	I
G/E	0.5232	ambiguous	0.5058	ambiguous	-0.975	Destabilizing	0.709	D	0.818	deleterious	N	0.520716604	None	None	I
G/F	0.8077	likely_pathogenic	0.7881	pathogenic	-1.261	Destabilizing	0.98	D	0.803	deleterious	None	None	None	None	I
G/H	0.6732	likely_pathogenic	0.686	pathogenic	-0.758	Destabilizing	0.98	D	0.803	deleterious	None	None	None	None	I
G/I	0.672	likely_pathogenic	0.6247	pathogenic	-0.56	Destabilizing	0.866	D	0.805	deleterious	None	None	None	None	I
G/K	0.6972	likely_pathogenic	0.7041	pathogenic	-0.798	Destabilizing	0.764	D	0.815	deleterious	None	None	None	None	I
G/L	0.6404	likely_pathogenic	0.5856	pathogenic	-0.56	Destabilizing	0.866	D	0.799	deleterious	None	None	None	None	I
G/M	0.6618	likely_pathogenic	0.6168	pathogenic	-0.388	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	I
G/N	0.5742	likely_pathogenic	0.5577	ambiguous	-0.47	Destabilizing	0.764	D	0.8	deleterious	None	None	None	None	I
G/P	0.9885	likely_pathogenic	0.9844	pathogenic	-0.495	Destabilizing	0.866	D	0.813	deleterious	None	None	None	None	I
G/Q	0.5704	likely_pathogenic	0.5678	pathogenic	-0.812	Destabilizing	0.866	D	0.815	deleterious	None	None	None	None	I
G/R	0.5581	ambiguous	0.5658	pathogenic	-0.369	Destabilizing	0.83	D	0.819	deleterious	N	0.510672969	None	None	I
G/S	0.1213	likely_benign	0.114	benign	-0.623	Destabilizing	0.013	N	0.516	neutral	None	None	None	None	I
G/T	0.3285	likely_benign	0.2907	benign	-0.721	Destabilizing	0.764	D	0.789	deleterious	None	None	None	None	I
G/V	0.4937	ambiguous	0.45	ambiguous	-0.495	Destabilizing	0.83	D	0.801	deleterious	N	0.517639014	None	None	I
G/W	0.6959	likely_pathogenic	0.6994	pathogenic	-1.391	Destabilizing	0.991	D	0.809	deleterious	N	0.501040971	None	None	I
G/Y	0.7273	likely_pathogenic	0.7183	pathogenic	-1.03	Destabilizing	0.98	D	0.81	deleterious	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.