TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25476	76651;76652;76653	chr2:178569706;178569705;178569704	chr2:179434433;179434432;179434431
N2AB	23835	71728;71729;71730	chr2:178569706;178569705;178569704	chr2:179434433;179434432;179434431
N2A	22908	68947;68948;68949	chr2:178569706;178569705;178569704	chr2:179434433;179434432;179434431
N2B	16411	49456;49457;49458	chr2:178569706;178569705;178569704	chr2:179434433;179434432;179434431
Novex-1	16536	49831;49832;49833	chr2:178569706;178569705;178569704	chr2:179434433;179434432;179434431
Novex-2	16603	50032;50033;50034	chr2:178569706;178569705;178569704	chr2:179434433;179434432;179434431
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: Fn3-73
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.2828
• 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/D	None	None	0.958	N	0.403	0.21	0.303781844768	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs868426391	None	0.958	N	0.464	0.284	0.295623431141	gnomAD-4.0.0	1.36908E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.31587E-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
E/A	0.1242	likely_benign	0.12	benign	-1.047	Destabilizing	0.919	D	0.541	neutral	N	0.479650898	None	None	N
E/C	0.7568	likely_pathogenic	0.7509	pathogenic	-0.633	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/D	0.2633	likely_benign	0.2642	benign	-1.337	Destabilizing	0.958	D	0.403	neutral	N	0.47321889	None	None	N
E/F	0.7489	likely_pathogenic	0.7515	pathogenic	-0.437	Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
E/G	0.1845	likely_benign	0.178	benign	-1.478	Destabilizing	0.988	D	0.722	prob.delet.	N	0.488311405	None	None	N
E/H	0.4378	ambiguous	0.4184	ambiguous	-0.809	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.3098	likely_benign	0.3077	benign	0.161	Stabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
E/K	0.1089	likely_benign	0.1075	benign	-1.203	Destabilizing	0.958	D	0.464	neutral	N	0.475318804	None	None	N
E/L	0.3724	ambiguous	0.3621	ambiguous	0.161	Stabilizing	0.982	D	0.742	deleterious	None	None	None	None	N
E/M	0.3749	ambiguous	0.366	ambiguous	0.803	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/N	0.3024	likely_benign	0.3009	benign	-1.596	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	N
E/P	0.445	ambiguous	0.449	ambiguous	-0.222	Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
E/Q	0.103	likely_benign	0.0988	benign	-1.363	Destabilizing	0.994	D	0.609	neutral	N	0.470243149	None	None	N
E/R	0.2103	likely_benign	0.2019	benign	-0.972	Destabilizing	0.991	D	0.688	prob.neutral	None	None	None	None	N
E/S	0.1863	likely_benign	0.1856	benign	-2.099	Highly Destabilizing	0.938	D	0.478	neutral	None	None	None	None	N
E/T	0.176	likely_benign	0.177	benign	-1.729	Destabilizing	0.086	N	0.346	neutral	None	None	None	None	N
E/V	0.188	likely_benign	0.1884	benign	-0.222	Destabilizing	0.976	D	0.715	prob.delet.	N	0.486096133	None	None	N
E/W	0.9223	likely_pathogenic	0.9157	pathogenic	-0.3	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/Y	0.6399	likely_pathogenic	0.6308	pathogenic	-0.221	Destabilizing	0.998	D	0.795	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.