TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30622	92089;92090;92091	chr2:178549858;178549857;178549856	chr2:179414585;179414584;179414583
N2AB	28981	87166;87167;87168	chr2:178549858;178549857;178549856	chr2:179414585;179414584;179414583
N2A	28054	84385;84386;84387	chr2:178549858;178549857;178549856	chr2:179414585;179414584;179414583
N2B	21557	64894;64895;64896	chr2:178549858;178549857;178549856	chr2:179414585;179414584;179414583
Novex-1	21682	65269;65270;65271	chr2:178549858;178549857;178549856	chr2:179414585;179414584;179414583
Novex-2	21749	65470;65471;65472	chr2:178549858;178549857;178549856	chr2:179414585;179414584;179414583
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-111
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2605
• 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
K/E	rs756685124	None	0.002	N	0.199	0.148	0.173771789658	gnomAD-4.0.0	4.95021E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.42002E-06	0	0
K/N	None	None	0.351	N	0.471	0.077	0.104622674875	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	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
K/A	0.1694	likely_benign	0.2159	benign	-0.402	Destabilizing	0.129	N	0.381	neutral	None	None	None	None	I
K/C	0.4855	ambiguous	0.5543	ambiguous	-0.553	Destabilizing	0.983	D	0.589	neutral	None	None	None	None	I
K/D	0.3586	ambiguous	0.4414	ambiguous	0.086	Stabilizing	0.264	N	0.437	neutral	None	None	None	None	I
K/E	0.1038	likely_benign	0.1291	benign	0.183	Stabilizing	0.002	N	0.199	neutral	N	0.513878272	None	None	I
K/F	0.5675	likely_pathogenic	0.7058	pathogenic	-0.085	Destabilizing	0.716	D	0.584	neutral	None	None	None	None	I
K/G	0.3292	likely_benign	0.3904	ambiguous	-0.743	Destabilizing	0.418	N	0.525	neutral	None	None	None	None	I
K/H	0.2586	likely_benign	0.3055	benign	-0.954	Destabilizing	0.836	D	0.567	neutral	None	None	None	None	I
K/I	0.1768	likely_benign	0.282	benign	0.466	Stabilizing	0.004	N	0.47	neutral	N	0.513531555	None	None	I
K/L	0.1928	likely_benign	0.2749	benign	0.466	Stabilizing	0.049	N	0.486	neutral	None	None	None	None	I
K/M	0.1434	likely_benign	0.1878	benign	0.17	Stabilizing	0.716	D	0.568	neutral	None	None	None	None	I
K/N	0.2345	likely_benign	0.3197	benign	-0.345	Destabilizing	0.351	N	0.471	neutral	N	0.495465869	None	None	I
K/P	0.2022	likely_benign	0.2421	benign	0.207	Stabilizing	None	N	0.287	neutral	None	None	None	None	I
K/Q	0.1013	likely_benign	0.1142	benign	-0.401	Destabilizing	0.007	N	0.346	neutral	N	0.51301148	None	None	I
K/R	0.0806	likely_benign	0.0815	benign	-0.504	Destabilizing	0.213	N	0.429	neutral	N	0.484344798	None	None	I
K/S	0.2404	likely_benign	0.3175	benign	-0.977	Destabilizing	0.129	N	0.381	neutral	None	None	None	None	I
K/T	0.1137	likely_benign	0.1544	benign	-0.683	Destabilizing	0.351	N	0.452	neutral	N	0.513358197	None	None	I
K/V	0.1543	likely_benign	0.2238	benign	0.207	Stabilizing	0.049	N	0.487	neutral	None	None	None	None	I
K/W	0.6982	likely_pathogenic	0.7761	pathogenic	0.022	Stabilizing	0.983	D	0.6	neutral	None	None	None	None	I
K/Y	0.471	ambiguous	0.5709	pathogenic	0.296	Stabilizing	0.836	D	0.601	neutral	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.