TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19444	58555;58556;58557	chr2:178594063;178594062;178594061	chr2:179458790;179458789;179458788
N2AB	17803	53632;53633;53634	chr2:178594063;178594062;178594061	chr2:179458790;179458789;179458788
N2A	16876	50851;50852;50853	chr2:178594063;178594062;178594061	chr2:179458790;179458789;179458788
N2B	10379	31360;31361;31362	chr2:178594063;178594062;178594061	chr2:179458790;179458789;179458788
Novex-1	10504	31735;31736;31737	chr2:178594063;178594062;178594061	chr2:179458790;179458789;179458788
Novex-2	10571	31936;31937;31938	chr2:178594063;178594062;178594061	chr2:179458790;179458789;179458788
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-118
• Domain position: 54
• Structural Position: 138
• Q(SASA): 0.3575
• 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/S	rs1239800877	None	1.0	D	0.893	0.711	0.742624401447	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/S	rs1239800877	None	1.0	D	0.893	0.711	0.742624401447	gnomAD-4.0.0	6.57618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47085E-05	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
L/A	0.8685	likely_pathogenic	0.8439	pathogenic	-2.407	Highly Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
L/C	0.8379	likely_pathogenic	0.8318	pathogenic	-1.746	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.9977	pathogenic	-3.008	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/E	0.9862	likely_pathogenic	0.9837	pathogenic	-2.708	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/F	0.2061	likely_benign	0.2176	benign	-1.459	Destabilizing	0.64	D	0.575	neutral	N	0.511000558	None	None	N
L/G	0.9764	likely_pathogenic	0.9725	pathogenic	-2.996	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/H	0.9476	likely_pathogenic	0.9412	pathogenic	-2.576	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/I	0.1537	likely_benign	0.1508	benign	-0.659	Destabilizing	0.996	D	0.713	prob.delet.	N	0.508176174	None	None	N
L/K	0.9717	likely_pathogenic	0.9648	pathogenic	-1.852	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/M	0.2108	likely_benign	0.2145	benign	-0.763	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/N	0.9898	likely_pathogenic	0.9883	pathogenic	-2.459	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/P	0.9866	likely_pathogenic	0.9872	pathogenic	-1.229	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/Q	0.9339	likely_pathogenic	0.9224	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/R	0.9457	likely_pathogenic	0.9312	pathogenic	-1.883	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/S	0.9721	likely_pathogenic	0.9655	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.548249479	None	None	N
L/T	0.9118	likely_pathogenic	0.9009	pathogenic	-2.617	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/V	0.1768	likely_benign	0.1663	benign	-1.229	Destabilizing	0.996	D	0.723	prob.delet.	N	0.517014492	None	None	N
L/W	0.6649	likely_pathogenic	0.6654	pathogenic	-1.828	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/Y	0.7788	likely_pathogenic	0.7894	pathogenic	-1.53	Destabilizing	0.998	D	0.857	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.