TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28313	85162;85163;85164	chr2:178561195;178561194;178561193	chr2:179425922;179425921;179425920
N2AB	26672	80239;80240;80241	chr2:178561195;178561194;178561193	chr2:179425922;179425921;179425920
N2A	25745	77458;77459;77460	chr2:178561195;178561194;178561193	chr2:179425922;179425921;179425920
N2B	19248	57967;57968;57969	chr2:178561195;178561194;178561193	chr2:179425922;179425921;179425920
Novex-1	19373	58342;58343;58344	chr2:178561195;178561194;178561193	chr2:179425922;179425921;179425920
Novex-2	19440	58543;58544;58545	chr2:178561195;178561194;178561193	chr2:179425922;179425921;179425920
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-94
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.5777
• 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
E/G	rs896539539	None	0.801	N	0.563	0.246	0.357929162469	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85809E-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
E/A	0.2435	likely_benign	0.2051	benign	-1.016	Destabilizing	0.801	D	0.527	neutral	N	0.471997151	None	None	N
E/C	0.8541	likely_pathogenic	0.8308	pathogenic	-0.42	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
E/D	0.1643	likely_benign	0.1354	benign	-0.864	Destabilizing	0.002	N	0.221	neutral	N	0.451083161	None	None	N
E/F	0.8605	likely_pathogenic	0.8203	pathogenic	-0.223	Destabilizing	0.991	D	0.62	neutral	None	None	None	None	N
E/G	0.4367	ambiguous	0.3621	ambiguous	-1.396	Destabilizing	0.801	D	0.563	neutral	N	0.517038794	None	None	N
E/H	0.5715	likely_pathogenic	0.4985	ambiguous	-0.281	Destabilizing	0.991	D	0.55	neutral	None	None	None	None	N
E/I	0.4119	ambiguous	0.3588	ambiguous	0.036	Stabilizing	0.974	D	0.633	neutral	None	None	None	None	N
E/K	0.3177	likely_benign	0.2542	benign	-0.25	Destabilizing	0.801	D	0.527	neutral	N	0.414469	None	None	N
E/L	0.4666	ambiguous	0.4124	ambiguous	0.036	Stabilizing	0.974	D	0.613	neutral	None	None	None	None	N
E/M	0.5351	ambiguous	0.4963	ambiguous	0.505	Stabilizing	0.998	D	0.615	neutral	None	None	None	None	N
E/N	0.3456	ambiguous	0.2853	benign	-0.989	Destabilizing	0.728	D	0.511	neutral	None	None	None	None	N
E/P	0.7321	likely_pathogenic	0.674	pathogenic	-0.295	Destabilizing	0.974	D	0.594	neutral	None	None	None	None	N
E/Q	0.2009	likely_benign	0.1811	benign	-0.828	Destabilizing	0.891	D	0.525	neutral	N	0.466801975	None	None	N
E/R	0.4509	ambiguous	0.3808	ambiguous	0.05	Stabilizing	0.974	D	0.563	neutral	None	None	None	None	N
E/S	0.2865	likely_benign	0.2421	benign	-1.312	Destabilizing	0.688	D	0.507	neutral	None	None	None	None	N
E/T	0.209	likely_benign	0.1762	benign	-0.965	Destabilizing	0.842	D	0.513	neutral	None	None	None	None	N
E/V	0.2346	likely_benign	0.2062	benign	-0.295	Destabilizing	0.966	D	0.619	neutral	N	0.433324119	None	None	N
E/W	0.9515	likely_pathogenic	0.9349	pathogenic	0.185	Stabilizing	0.998	D	0.67	neutral	None	None	None	None	N
E/Y	0.7661	likely_pathogenic	0.7002	pathogenic	0.106	Stabilizing	0.991	D	0.624	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.