TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22429	67510;67511;67512	chr2:178580002;178580001;178580000	chr2:179444729;179444728;179444727
N2AB	20788	62587;62588;62589	chr2:178580002;178580001;178580000	chr2:179444729;179444728;179444727
N2A	19861	59806;59807;59808	chr2:178580002;178580001;178580000	chr2:179444729;179444728;179444727
N2B	13364	40315;40316;40317	chr2:178580002;178580001;178580000	chr2:179444729;179444728;179444727
Novex-1	13489	40690;40691;40692	chr2:178580002;178580001;178580000	chr2:179444729;179444728;179444727
Novex-2	13556	40891;40892;40893	chr2:178580002;178580001;178580000	chr2:179444729;179444728;179444727
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-50
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.1014
• 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
F/L	rs879180662	-1.843	None	N	0.194	0.284	0.260249123532	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
F/L	rs879180662	-1.843	None	N	0.194	0.284	0.260249123532	gnomAD-4.0.0	3.18462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86017E-06	0	3.02627E-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
F/A	0.4806	ambiguous	0.4758	ambiguous	-3.268	Highly Destabilizing	0.103	N	0.641	neutral	None	None	None	None	N
F/C	0.2663	likely_benign	0.2399	benign	-1.793	Destabilizing	0.954	D	0.679	prob.neutral	N	0.482520789	None	None	N
F/D	0.8925	likely_pathogenic	0.8698	pathogenic	-3.362	Highly Destabilizing	0.561	D	0.696	prob.neutral	None	None	None	None	N
F/E	0.8738	likely_pathogenic	0.8403	pathogenic	-3.214	Highly Destabilizing	0.561	D	0.682	prob.neutral	None	None	None	None	N
F/G	0.8165	likely_pathogenic	0.8029	pathogenic	-3.638	Highly Destabilizing	0.39	N	0.682	prob.neutral	None	None	None	None	N
F/H	0.6434	likely_pathogenic	0.5815	pathogenic	-1.911	Destabilizing	0.965	D	0.693	prob.neutral	None	None	None	None	N
F/I	0.4013	ambiguous	0.3855	ambiguous	-2.06	Highly Destabilizing	0.166	N	0.525	neutral	N	0.448253499	None	None	N
F/K	0.9076	likely_pathogenic	0.9079	pathogenic	-2.173	Highly Destabilizing	0.561	D	0.695	prob.neutral	None	None	None	None	N
F/L	0.7316	likely_pathogenic	0.6643	pathogenic	-2.06	Highly Destabilizing	None	N	0.194	neutral	N	0.369966074	None	None	N
F/M	0.3989	ambiguous	0.3595	ambiguous	-1.588	Destabilizing	0.818	D	0.657	neutral	None	None	None	None	N
F/N	0.7082	likely_pathogenic	0.6627	pathogenic	-2.45	Highly Destabilizing	0.561	D	0.713	prob.delet.	None	None	None	None	N
F/P	0.9986	likely_pathogenic	0.9986	pathogenic	-2.472	Highly Destabilizing	0.901	D	0.725	prob.delet.	None	None	None	None	N
F/Q	0.7742	likely_pathogenic	0.7354	pathogenic	-2.559	Highly Destabilizing	0.818	D	0.727	prob.delet.	None	None	None	None	N
F/R	0.8135	likely_pathogenic	0.8145	pathogenic	-1.382	Destabilizing	0.818	D	0.718	prob.delet.	None	None	None	None	N
F/S	0.328	likely_benign	0.3183	benign	-3.076	Highly Destabilizing	0.005	N	0.5	neutral	N	0.39168814	None	None	N
F/T	0.4591	ambiguous	0.4265	ambiguous	-2.842	Highly Destabilizing	0.209	N	0.66	neutral	None	None	None	None	N
F/V	0.3549	ambiguous	0.3341	benign	-2.472	Highly Destabilizing	0.166	N	0.643	neutral	N	0.436420353	None	None	N
F/W	0.5859	likely_pathogenic	0.5688	pathogenic	-0.874	Destabilizing	0.991	D	0.665	neutral	None	None	None	None	N
F/Y	0.1932	likely_benign	0.1788	benign	-1.261	Destabilizing	0.856	D	0.567	neutral	N	0.458142419	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.