TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16614	50065;50066;50067	chr2:178612881;178612880;178612879	chr2:179477608;179477607;179477606
N2AB	14973	45142;45143;45144	chr2:178612881;178612880;178612879	chr2:179477608;179477607;179477606
N2A	14046	42361;42362;42363	chr2:178612881;178612880;178612879	chr2:179477608;179477607;179477606
N2B	7549	22870;22871;22872	chr2:178612881;178612880;178612879	chr2:179477608;179477607;179477606
Novex-1	7674	23245;23246;23247	chr2:178612881;178612880;178612879	chr2:179477608;179477607;179477606
Novex-2	7741	23446;23447;23448	chr2:178612881;178612880;178612879	chr2:179477608;179477607;179477606
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: Fn3-8
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.45
• 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
G/V	None	None	0.999	D	0.797	0.442	0.585140355757	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
G/A	0.2506	likely_benign	0.2358	benign	-0.201	Destabilizing	0.995	D	0.634	neutral	D	0.585947868	None	None	N
G/C	0.441	ambiguous	0.4136	ambiguous	-0.875	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/D	0.2706	likely_benign	0.327	benign	-0.524	Destabilizing	0.669	D	0.508	neutral	None	None	None	None	N
G/E	0.3559	ambiguous	0.4008	ambiguous	-0.684	Destabilizing	0.997	D	0.774	deleterious	N	0.50983174	None	None	N
G/F	0.7461	likely_pathogenic	0.7362	pathogenic	-0.936	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/H	0.5198	ambiguous	0.5582	ambiguous	-0.39	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/I	0.6288	likely_pathogenic	0.6092	pathogenic	-0.367	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/K	0.5887	likely_pathogenic	0.6668	pathogenic	-0.742	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
G/L	0.6344	likely_pathogenic	0.625	pathogenic	-0.367	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
G/M	0.6571	likely_pathogenic	0.6393	pathogenic	-0.493	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
G/N	0.2912	likely_benign	0.2985	benign	-0.396	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
G/P	0.9383	likely_pathogenic	0.9432	pathogenic	-0.28	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
G/Q	0.4385	ambiguous	0.4904	ambiguous	-0.67	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
G/R	0.4932	ambiguous	0.5592	ambiguous	-0.3	Destabilizing	0.999	D	0.793	deleterious	N	0.503137406	None	None	N
G/S	0.1539	likely_benign	0.1467	benign	-0.543	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
G/T	0.3055	likely_benign	0.3012	benign	-0.631	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
G/V	0.4658	ambiguous	0.4511	ambiguous	-0.28	Destabilizing	0.999	D	0.797	deleterious	D	0.7108338	None	None	N
G/W	0.6877	likely_pathogenic	0.7121	pathogenic	-1.087	Destabilizing	1.0	D	0.757	deleterious	D	0.7109366	None	None	N
G/Y	0.6191	likely_pathogenic	0.6291	pathogenic	-0.737	Destabilizing	1.0	D	0.796	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.