TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13876	41851;41852;41853	chr2:178635698;178635697;178635696	chr2:179500425;179500424;179500423
N2AB	12235	36928;36929;36930	chr2:178635698;178635697;178635696	chr2:179500425;179500424;179500423
N2A	11308	34147;34148;34149	chr2:178635698;178635697;178635696	chr2:179500425;179500424;179500423
N2B	4811	14656;14657;14658	chr2:178635698;178635697;178635696	chr2:179500425;179500424;179500423
Novex-1	4936	15031;15032;15033	chr2:178635698;178635697;178635696	chr2:179500425;179500424;179500423
Novex-2	5003	15232;15233;15234	chr2:178635698;178635697;178635696	chr2:179500425;179500424;179500423
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-89
• Domain position: 1
• Structural Position: 3
• Q(SASA): 0.0892
• 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/M	None	None	0.997	N	0.697	0.144	0.422524665647	gnomAD-4.0.0	1.62411E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9098E-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	0.8935	likely_pathogenic	0.9247	pathogenic	-2.049	Highly Destabilizing	0.991	D	0.608	neutral	None	None	None	None	N
L/C	0.9284	likely_pathogenic	0.9482	pathogenic	-1.212	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/D	0.9965	likely_pathogenic	0.9977	pathogenic	-1.795	Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
L/E	0.9754	likely_pathogenic	0.9842	pathogenic	-1.697	Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
L/F	0.7159	likely_pathogenic	0.7923	pathogenic	-1.312	Destabilizing	0.283	N	0.443	neutral	None	None	None	None	N
L/G	0.9827	likely_pathogenic	0.9884	pathogenic	-2.439	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
L/H	0.9604	likely_pathogenic	0.9744	pathogenic	-1.51	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/I	0.2533	likely_benign	0.306	benign	-0.988	Destabilizing	0.422	N	0.243	neutral	None	None	None	None	N
L/K	0.9594	likely_pathogenic	0.9727	pathogenic	-1.479	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
L/M	0.3784	ambiguous	0.4334	ambiguous	-0.863	Destabilizing	0.997	D	0.697	prob.delet.	N	0.505204106	None	None	N
L/N	0.9798	likely_pathogenic	0.9863	pathogenic	-1.457	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/P	0.9791	likely_pathogenic	0.9813	pathogenic	-1.317	Destabilizing	0.999	D	0.867	deleterious	N	0.506796605	None	None	N
L/Q	0.9326	likely_pathogenic	0.9578	pathogenic	-1.525	Destabilizing	0.999	D	0.814	deleterious	N	0.506796605	None	None	N
L/R	0.9343	likely_pathogenic	0.9579	pathogenic	-0.968	Destabilizing	0.999	D	0.825	deleterious	N	0.505411417	None	None	N
L/S	0.9824	likely_pathogenic	0.9896	pathogenic	-2.062	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
L/T	0.9193	likely_pathogenic	0.9461	pathogenic	-1.833	Destabilizing	0.997	D	0.728	deleterious	None	None	None	None	N
L/V	0.3359	likely_benign	0.3995	ambiguous	-1.317	Destabilizing	0.894	D	0.555	neutral	N	0.444613255	None	None	N
L/W	0.9193	likely_pathogenic	0.9457	pathogenic	-1.423	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/Y	0.9478	likely_pathogenic	0.9645	pathogenic	-1.205	Destabilizing	0.99	D	0.753	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.