TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9200	27823;27824;27825	chr2:178712324;178712323;178712322	chr2:179577051;179577050;179577049
N2AB	8883	26872;26873;26874	chr2:178712324;178712323;178712322	chr2:179577051;179577050;179577049
N2A	7956	24091;24092;24093	chr2:178712324;178712323;178712322	chr2:179577051;179577050;179577049
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-77
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3772
• 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
L/F	None	None	0.966	N	0.329	0.148	0.321951552304	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43353E-05	0
L/P	rs776598104	None	0.966	N	0.368	0.315	0.495506531988	gnomAD-4.0.0	1.36927E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80009E-06	0	0
L/R	rs776598104	0.177	0.876	N	0.346	0.272	0.430126000877	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
L/R	rs776598104	0.177	0.876	N	0.346	0.272	0.430126000877	gnomAD-4.0.0	2.0539E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73491E-04	0	2.32024E-05	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
L/A	0.0982	likely_benign	0.1015	benign	-0.958	Destabilizing	0.525	D	0.269	neutral	None	None	None	None	N
L/C	0.2576	likely_benign	0.2682	benign	-0.739	Destabilizing	0.998	D	0.317	neutral	None	None	None	None	N
L/D	0.2567	likely_benign	0.2601	benign	-0.139	Destabilizing	0.842	D	0.348	neutral	None	None	None	None	N
L/E	0.1534	likely_benign	0.1493	benign	-0.174	Destabilizing	0.728	D	0.327	neutral	None	None	None	None	N
L/F	0.0651	likely_benign	0.0683	benign	-0.628	Destabilizing	0.966	D	0.329	neutral	N	0.455304397	None	None	N
L/G	0.2477	likely_benign	0.2578	benign	-1.202	Destabilizing	0.728	D	0.315	neutral	None	None	None	None	N
L/H	0.0817	likely_benign	0.0845	benign	-0.33	Destabilizing	0.991	D	0.357	neutral	N	0.477391823	None	None	N
L/I	0.0589	likely_benign	0.0612	benign	-0.406	Destabilizing	0.801	D	0.225	neutral	N	0.441065663	None	None	N
L/K	0.1205	likely_benign	0.1197	benign	-0.567	Destabilizing	0.728	D	0.303	neutral	None	None	None	None	N
L/M	0.0719	likely_benign	0.0767	benign	-0.461	Destabilizing	0.974	D	0.371	neutral	None	None	None	None	N
L/N	0.1219	likely_benign	0.1229	benign	-0.445	Destabilizing	0.842	D	0.346	neutral	None	None	None	None	N
L/P	0.689	likely_pathogenic	0.6189	pathogenic	-0.556	Destabilizing	0.966	D	0.368	neutral	N	0.461047712	None	None	N
L/Q	0.0715	likely_benign	0.0697	benign	-0.604	Destabilizing	0.142	N	0.249	neutral	None	None	None	None	N
L/R	0.0932	likely_benign	0.0913	benign	-0.023	Destabilizing	0.876	D	0.346	neutral	N	0.454514963	None	None	N
L/S	0.0782	likely_benign	0.0807	benign	-1.015	Destabilizing	0.029	N	0.203	neutral	None	None	None	None	N
L/T	0.0722	likely_benign	0.0745	benign	-0.934	Destabilizing	0.067	N	0.196	neutral	None	None	None	None	N
L/V	0.0587	likely_benign	0.0608	benign	-0.556	Destabilizing	0.454	N	0.233	neutral	N	0.410532112	None	None	N
L/W	0.1282	likely_benign	0.1303	benign	-0.658	Destabilizing	0.998	D	0.388	neutral	None	None	None	None	N
L/Y	0.1361	likely_benign	0.1474	benign	-0.424	Destabilizing	0.991	D	0.339	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.