TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33330	100213;100214;100215	chr2:178537121;178537120;178537119	chr2:179401848;179401847;179401846
N2AB	31689	95290;95291;95292	chr2:178537121;178537120;178537119	chr2:179401848;179401847;179401846
N2A	30762	92509;92510;92511	chr2:178537121;178537120;178537119	chr2:179401848;179401847;179401846
N2B	24265	73018;73019;73020	chr2:178537121;178537120;178537119	chr2:179401848;179401847;179401846
Novex-1	24390	73393;73394;73395	chr2:178537121;178537120;178537119	chr2:179401848;179401847;179401846
Novex-2	24457	73594;73595;73596	chr2:178537121;178537120;178537119	chr2:179401848;179401847;179401846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-130
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.1048
• 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
K/I	None	None	0.997	N	0.89	0.45	0.52586976336	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.9538	likely_pathogenic	0.9287	pathogenic	-1.42	Destabilizing	0.983	D	0.727	prob.delet.	None	None	None	None	N
K/C	0.9372	likely_pathogenic	0.9252	pathogenic	-1.527	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
K/D	0.9969	likely_pathogenic	0.9954	pathogenic	-2.426	Highly Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
K/E	0.9466	likely_pathogenic	0.922	pathogenic	-2.09	Highly Destabilizing	0.977	D	0.671	neutral	N	0.506109264	None	None	N
K/F	0.9794	likely_pathogenic	0.9717	pathogenic	-0.648	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
K/G	0.9814	likely_pathogenic	0.9739	pathogenic	-1.915	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
K/H	0.857	likely_pathogenic	0.8405	pathogenic	-1.614	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
K/I	0.8402	likely_pathogenic	0.7476	pathogenic	0.009	Stabilizing	0.997	D	0.89	deleterious	N	0.474620787	None	None	N
K/L	0.8694	likely_pathogenic	0.8342	pathogenic	0.009	Stabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
K/M	0.7299	likely_pathogenic	0.6418	pathogenic	-0.416	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/N	0.9831	likely_pathogenic	0.9751	pathogenic	-2.102	Highly Destabilizing	0.993	D	0.777	deleterious	D	0.528821875	None	None	N
K/P	0.9993	likely_pathogenic	0.9989	pathogenic	-0.451	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
K/Q	0.6848	likely_pathogenic	0.6364	pathogenic	-1.65	Destabilizing	0.993	D	0.779	deleterious	N	0.469900754	None	None	N
K/R	0.1792	likely_benign	0.1953	benign	-0.957	Destabilizing	0.235	N	0.408	neutral	N	0.483598224	None	None	N
K/S	0.9795	likely_pathogenic	0.9701	pathogenic	-2.535	Highly Destabilizing	0.983	D	0.671	neutral	None	None	None	None	N
K/T	0.8853	likely_pathogenic	0.8215	pathogenic	-1.934	Destabilizing	0.997	D	0.773	deleterious	N	0.491510501	None	None	N
K/V	0.826	likely_pathogenic	0.7395	pathogenic	-0.451	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
K/W	0.9831	likely_pathogenic	0.9808	pathogenic	-0.777	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
K/Y	0.9225	likely_pathogenic	0.8992	pathogenic	-0.42	Destabilizing	0.999	D	0.868	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.