TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28615	86068;86069;86070	chr2:178560289;178560288;178560287	chr2:179425016;179425015;179425014
N2AB	26974	81145;81146;81147	chr2:178560289;178560288;178560287	chr2:179425016;179425015;179425014
N2A	26047	78364;78365;78366	chr2:178560289;178560288;178560287	chr2:179425016;179425015;179425014
N2B	19550	58873;58874;58875	chr2:178560289;178560288;178560287	chr2:179425016;179425015;179425014
Novex-1	19675	59248;59249;59250	chr2:178560289;178560288;178560287	chr2:179425016;179425015;179425014
Novex-2	19742	59449;59450;59451	chr2:178560289;178560288;178560287	chr2:179425016;179425015;179425014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-96
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1264
• 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	rs978201175	None	1.0	D	0.868	0.648	0.858355847791	gnomAD-4.0.0	2.7368E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59786E-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
L/A	0.9433	likely_pathogenic	0.9442	pathogenic	-2.561	Highly Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
L/C	0.8978	likely_pathogenic	0.9075	pathogenic	-1.969	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/D	0.9984	likely_pathogenic	0.9989	pathogenic	-2.643	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/E	0.9878	likely_pathogenic	0.9911	pathogenic	-2.541	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/F	0.7053	likely_pathogenic	0.7117	pathogenic	-1.833	Destabilizing	1.0	D	0.868	deleterious	D	0.658475631	None	None	N
L/G	0.9835	likely_pathogenic	0.9848	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/H	0.9623	likely_pathogenic	0.9688	pathogenic	-2.207	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.68482096	None	None	N
L/I	0.293	likely_benign	0.3023	benign	-1.329	Destabilizing	0.999	D	0.821	deleterious	D	0.645626213	None	None	N
L/K	0.9716	likely_pathogenic	0.9795	pathogenic	-1.876	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/M	0.3877	ambiguous	0.3903	ambiguous	-1.134	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/N	0.976	likely_pathogenic	0.9805	pathogenic	-1.957	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/P	0.9876	likely_pathogenic	0.9896	pathogenic	-1.716	Destabilizing	1.0	D	0.857	deleterious	D	0.68482096	None	None	N
L/Q	0.9263	likely_pathogenic	0.9396	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/R	0.9519	likely_pathogenic	0.9648	pathogenic	-1.283	Destabilizing	1.0	D	0.856	deleterious	D	0.659282848	None	None	N
L/S	0.9821	likely_pathogenic	0.9837	pathogenic	-2.655	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/T	0.9404	likely_pathogenic	0.9462	pathogenic	-2.42	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/V	0.3829	ambiguous	0.387	ambiguous	-1.716	Destabilizing	0.999	D	0.825	deleterious	D	0.601161323	None	None	N
L/W	0.9494	likely_pathogenic	0.9604	pathogenic	-2.031	Highly Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/Y	0.9531	likely_pathogenic	0.9605	pathogenic	-1.812	Destabilizing	1.0	D	0.835	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.