TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23653	71182;71183;71184	chr2:178575175;178575174;178575173	chr2:179439902;179439901;179439900
N2AB	22012	66259;66260;66261	chr2:178575175;178575174;178575173	chr2:179439902;179439901;179439900
N2A	21085	63478;63479;63480	chr2:178575175;178575174;178575173	chr2:179439902;179439901;179439900
N2B	14588	43987;43988;43989	chr2:178575175;178575174;178575173	chr2:179439902;179439901;179439900
Novex-1	14713	44362;44363;44364	chr2:178575175;178575174;178575173	chr2:179439902;179439901;179439900
Novex-2	14780	44563;44564;44565	chr2:178575175;178575174;178575173	chr2:179439902;179439901;179439900
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-130
• Domain position: 17
• Structural Position: 30
• Q(SASA): 0.1111
• 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
V/A	None	None	0.977	N	0.668	0.445	0.605774515499	gnomAD-4.0.0	1.59373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86144E-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
V/A	0.4263	ambiguous	0.5226	ambiguous	-1.932	Destabilizing	0.977	D	0.668	neutral	N	0.483579643	None	None	N
V/C	0.8891	likely_pathogenic	0.9221	pathogenic	-1.515	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/D	0.9879	likely_pathogenic	0.9915	pathogenic	-2.213	Highly Destabilizing	0.999	D	0.881	deleterious	N	0.495354022	None	None	N
V/E	0.9641	likely_pathogenic	0.9723	pathogenic	-2.008	Highly Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
V/F	0.4687	ambiguous	0.5182	ambiguous	-1.182	Destabilizing	0.993	D	0.843	deleterious	N	0.398539542	None	None	N
V/G	0.7737	likely_pathogenic	0.826	pathogenic	-2.413	Highly Destabilizing	0.999	D	0.883	deleterious	N	0.495354022	None	None	N
V/H	0.9873	likely_pathogenic	0.9912	pathogenic	-1.828	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/I	0.088	likely_benign	0.0908	benign	-0.6	Destabilizing	0.117	N	0.291	neutral	N	0.419117963	None	None	N
V/K	0.9779	likely_pathogenic	0.9818	pathogenic	-1.719	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
V/L	0.3293	likely_benign	0.3741	ambiguous	-0.6	Destabilizing	0.898	D	0.626	neutral	N	0.356114129	None	None	N
V/M	0.3141	likely_benign	0.3683	ambiguous	-0.661	Destabilizing	0.995	D	0.764	deleterious	None	None	None	None	N
V/N	0.9718	likely_pathogenic	0.9815	pathogenic	-2.046	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
V/P	0.9837	likely_pathogenic	0.9875	pathogenic	-1.017	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
V/Q	0.9669	likely_pathogenic	0.9748	pathogenic	-1.905	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
V/R	0.9659	likely_pathogenic	0.9715	pathogenic	-1.507	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
V/S	0.8796	likely_pathogenic	0.9223	pathogenic	-2.654	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
V/T	0.6045	likely_pathogenic	0.687	pathogenic	-2.295	Highly Destabilizing	0.983	D	0.769	deleterious	None	None	None	None	N
V/W	0.9711	likely_pathogenic	0.9791	pathogenic	-1.511	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/Y	0.914	likely_pathogenic	0.9309	pathogenic	-1.16	Destabilizing	0.999	D	0.833	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.