TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21330	64213;64214;64215	chr2:178587223;178587222;178587221	chr2:179451950;179451949;179451948
N2AB	19689	59290;59291;59292	chr2:178587223;178587222;178587221	chr2:179451950;179451949;179451948
N2A	18762	56509;56510;56511	chr2:178587223;178587222;178587221	chr2:179451950;179451949;179451948
N2B	12265	37018;37019;37020	chr2:178587223;178587222;178587221	chr2:179451950;179451949;179451948
Novex-1	12390	37393;37394;37395	chr2:178587223;178587222;178587221	chr2:179451950;179451949;179451948
Novex-2	12457	37594;37595;37596	chr2:178587223;178587222;178587221	chr2:179451950;179451949;179451948
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: Fn3-42
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.0992
• 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	rs778195959	-2.218	0.967	D	0.769	0.776	0.890950925297	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
L/F	rs778195959	-2.218	0.967	D	0.769	0.776	0.890950925297	gnomAD-4.0.0	6.15962E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09708E-06	0	0
L/P	rs2049213559	None	0.994	D	0.858	0.891	0.913711777733	gnomAD-4.0.0	3.18458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86582E-05	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	0.9448	likely_pathogenic	0.9325	pathogenic	-2.837	Highly Destabilizing	0.845	D	0.769	deleterious	None	None	None	None	N
L/C	0.9226	likely_pathogenic	0.9233	pathogenic	-2.62	Highly Destabilizing	0.154	N	0.739	prob.delet.	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9992	pathogenic	-3.544	Highly Destabilizing	0.996	D	0.855	deleterious	None	None	None	None	N
L/E	0.9974	likely_pathogenic	0.9965	pathogenic	-3.36	Highly Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
L/F	0.8335	likely_pathogenic	0.7763	pathogenic	-1.888	Destabilizing	0.967	D	0.769	deleterious	D	0.641991941	None	None	N
L/G	0.9929	likely_pathogenic	0.9897	pathogenic	-3.343	Highly Destabilizing	0.987	D	0.861	deleterious	None	None	None	None	N
L/H	0.9932	likely_pathogenic	0.99	pathogenic	-2.714	Highly Destabilizing	0.999	D	0.849	deleterious	D	0.658818519	None	None	N
L/I	0.2914	likely_benign	0.2852	benign	-1.38	Destabilizing	0.805	D	0.733	prob.delet.	D	0.611962338	None	None	N
L/K	0.996	likely_pathogenic	0.9937	pathogenic	-2.33	Highly Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	N
L/M	0.3312	likely_benign	0.3071	benign	-1.469	Destabilizing	0.496	N	0.541	neutral	None	None	None	None	N
L/N	0.9955	likely_pathogenic	0.9937	pathogenic	-2.702	Highly Destabilizing	0.996	D	0.867	deleterious	None	None	None	None	N
L/P	0.9931	likely_pathogenic	0.99	pathogenic	-1.848	Destabilizing	0.994	D	0.858	deleterious	D	0.658818519	None	None	N
L/Q	0.989	likely_pathogenic	0.9832	pathogenic	-2.651	Highly Destabilizing	0.987	D	0.82	deleterious	None	None	None	None	N
L/R	0.9906	likely_pathogenic	0.985	pathogenic	-1.869	Destabilizing	0.983	D	0.831	deleterious	D	0.642799158	None	None	N
L/S	0.9934	likely_pathogenic	0.9908	pathogenic	-3.36	Highly Destabilizing	0.975	D	0.812	deleterious	None	None	None	None	N
L/T	0.9318	likely_pathogenic	0.9176	pathogenic	-3.034	Highly Destabilizing	0.975	D	0.798	deleterious	None	None	None	None	N
L/V	0.2989	likely_benign	0.3241	benign	-1.848	Destabilizing	0.805	D	0.745	deleterious	D	0.581427327	None	None	N
L/W	0.9876	likely_pathogenic	0.9809	pathogenic	-2.256	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
L/Y	0.988	likely_pathogenic	0.9815	pathogenic	-2.031	Highly Destabilizing	0.996	D	0.788	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.