TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29928	90007;90008;90009	chr2:178553118;178553117;178553116	chr2:179417845;179417844;179417843
N2AB	28287	85084;85085;85086	chr2:178553118;178553117;178553116	chr2:179417845;179417844;179417843
N2A	27360	82303;82304;82305	chr2:178553118;178553117;178553116	chr2:179417845;179417844;179417843
N2B	20863	62812;62813;62814	chr2:178553118;178553117;178553116	chr2:179417845;179417844;179417843
Novex-1	20988	63187;63188;63189	chr2:178553118;178553117;178553116	chr2:179417845;179417844;179417843
Novex-2	21055	63388;63389;63390	chr2:178553118;178553117;178553116	chr2:179417845;179417844;179417843
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-147
• Domain position: 87
• Structural Position: 174
• Q(SASA): 0.1893
• 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
V/I	rs746336106	-0.466	0.948	N	0.573	0.144	0.468504517574	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
V/A	0.9362	likely_pathogenic	0.9161	pathogenic	-2.032	Highly Destabilizing	0.994	D	0.644	neutral	D	0.529699885	None	None	N
V/C	0.9646	likely_pathogenic	0.9524	pathogenic	-1.882	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.9978	pathogenic	-2.03	Highly Destabilizing	0.999	D	0.825	deleterious	D	0.530206865	None	None	N
V/E	0.9939	likely_pathogenic	0.9912	pathogenic	-1.847	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/F	0.4577	ambiguous	0.4178	ambiguous	-1.294	Destabilizing	0.997	D	0.781	deleterious	N	0.502441371	None	None	N
V/G	0.9675	likely_pathogenic	0.9575	pathogenic	-2.546	Highly Destabilizing	0.999	D	0.829	deleterious	N	0.518850559	None	None	N
V/H	0.9961	likely_pathogenic	0.9944	pathogenic	-2.14	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
V/I	0.0726	likely_benign	0.0706	benign	-0.626	Destabilizing	0.948	D	0.573	neutral	N	0.454783969	None	None	N
V/K	0.9926	likely_pathogenic	0.9893	pathogenic	-1.656	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/L	0.3501	ambiguous	0.2873	benign	-0.626	Destabilizing	0.104	N	0.326	neutral	N	0.434971118	None	None	N
V/M	0.4414	ambiguous	0.3964	ambiguous	-0.791	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
V/N	0.9936	likely_pathogenic	0.9909	pathogenic	-1.878	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/P	0.9965	likely_pathogenic	0.9943	pathogenic	-1.065	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/Q	0.9899	likely_pathogenic	0.9854	pathogenic	-1.767	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/R	0.9862	likely_pathogenic	0.9813	pathogenic	-1.443	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/S	0.9848	likely_pathogenic	0.9793	pathogenic	-2.615	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/T	0.9455	likely_pathogenic	0.928	pathogenic	-2.276	Highly Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
V/W	0.9871	likely_pathogenic	0.9823	pathogenic	-1.65	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/Y	0.9663	likely_pathogenic	0.9532	pathogenic	-1.296	Destabilizing	1.0	D	0.777	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.