TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22377	67354;67355;67356	chr2:178580158;178580157;178580156	chr2:179444885;179444884;179444883
N2AB	20736	62431;62432;62433	chr2:178580158;178580157;178580156	chr2:179444885;179444884;179444883
N2A	19809	59650;59651;59652	chr2:178580158;178580157;178580156	chr2:179444885;179444884;179444883
N2B	13312	40159;40160;40161	chr2:178580158;178580157;178580156	chr2:179444885;179444884;179444883
Novex-1	13437	40534;40535;40536	chr2:178580158;178580157;178580156	chr2:179444885;179444884;179444883
Novex-2	13504	40735;40736;40737	chr2:178580158;178580157;178580156	chr2:179444885;179444884;179444883
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-50
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4571
• Predicted PPI site: I

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
P/L	rs771093991	-0.572	0.976	N	0.747	0.473	0.75672024113	gnomAD-2.1.1	2.42E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.96143E-04	None	0	0	0
P/L	rs771093991	-0.572	0.976	N	0.747	0.473	0.75672024113	gnomAD-4.0.0	8.89758E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.50756E-04	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
P/A	0.0897	likely_benign	0.088	benign	-1.74	Destabilizing	0.067	N	0.295	neutral	N	0.488604186	None	None	I
P/C	0.6865	likely_pathogenic	0.643	pathogenic	-1.173	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
P/D	0.7368	likely_pathogenic	0.7444	pathogenic	-2.124	Highly Destabilizing	0.995	D	0.748	deleterious	None	None	None	None	I
P/E	0.4698	ambiguous	0.4688	ambiguous	-2.018	Highly Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	I
P/F	0.7037	likely_pathogenic	0.6807	pathogenic	-1.19	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	I
P/G	0.5114	ambiguous	0.5083	ambiguous	-2.126	Highly Destabilizing	0.938	D	0.639	neutral	None	None	None	None	I
P/H	0.4231	ambiguous	0.4018	ambiguous	-1.595	Destabilizing	0.999	D	0.791	deleterious	N	0.515688959	None	None	I
P/I	0.3412	ambiguous	0.3073	benign	-0.725	Destabilizing	0.991	D	0.819	deleterious	None	None	None	None	I
P/K	0.4851	ambiguous	0.4902	ambiguous	-1.622	Destabilizing	0.991	D	0.701	prob.neutral	None	None	None	None	I
P/L	0.1547	likely_benign	0.1449	benign	-0.725	Destabilizing	0.976	D	0.747	deleterious	N	0.503661091	None	None	I
P/M	0.2921	likely_benign	0.2602	benign	-0.639	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
P/N	0.4976	ambiguous	0.4906	ambiguous	-1.655	Destabilizing	0.995	D	0.817	deleterious	None	None	None	None	I
P/Q	0.2663	likely_benign	0.2533	benign	-1.701	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	I
P/R	0.4328	ambiguous	0.4309	ambiguous	-1.171	Destabilizing	0.994	D	0.805	deleterious	N	0.49419089	None	None	I
P/S	0.2026	likely_benign	0.1965	benign	-2.131	Highly Destabilizing	0.919	D	0.619	neutral	N	0.48718945	None	None	I
P/T	0.163	likely_benign	0.1563	benign	-1.905	Destabilizing	0.988	D	0.696	prob.neutral	N	0.503407601	None	None	I
P/V	0.2385	likely_benign	0.2177	benign	-1.034	Destabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	I
P/W	0.8948	likely_pathogenic	0.8805	pathogenic	-1.497	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/Y	0.6651	likely_pathogenic	0.6404	pathogenic	-1.163	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I

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.