TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30760	92503;92504;92505	chr2:178549348;178549347;178549346	chr2:179414075;179414074;179414073
N2AB	29119	87580;87581;87582	chr2:178549348;178549347;178549346	chr2:179414075;179414074;179414073
N2A	28192	84799;84800;84801	chr2:178549348;178549347;178549346	chr2:179414075;179414074;179414073
N2B	21695	65308;65309;65310	chr2:178549348;178549347;178549346	chr2:179414075;179414074;179414073
Novex-1	21820	65683;65684;65685	chr2:178549348;178549347;178549346	chr2:179414075;179414074;179414073
Novex-2	21887	65884;65885;65886	chr2:178549348;178549347;178549346	chr2:179414075;179414074;179414073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-112
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.4858
• 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
E/Q	rs936029222	-0.517	0.989	N	0.583	0.335	0.406806705197	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/Q	rs936029222	-0.517	0.989	N	0.583	0.335	0.406806705197	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	None	0	0	0	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
E/A	0.8383	likely_pathogenic	0.8485	pathogenic	-0.937	Destabilizing	0.039	N	0.299	neutral	N	0.477017552	None	None	N
E/C	0.9874	likely_pathogenic	0.9883	pathogenic	-0.517	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
E/D	0.4928	ambiguous	0.472	ambiguous	-1.254	Destabilizing	0.963	D	0.412	neutral	N	0.443407827	None	None	N
E/F	0.9915	likely_pathogenic	0.9917	pathogenic	-0.332	Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
E/G	0.7624	likely_pathogenic	0.7677	pathogenic	-1.336	Destabilizing	0.865	D	0.58	neutral	N	0.489387815	None	None	N
E/H	0.9651	likely_pathogenic	0.9681	pathogenic	-0.686	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
E/I	0.9569	likely_pathogenic	0.9594	pathogenic	0.167	Stabilizing	0.983	D	0.767	deleterious	None	None	None	None	N
E/K	0.8726	likely_pathogenic	0.8797	pathogenic	-0.767	Destabilizing	0.928	D	0.483	neutral	D	0.522367256	None	None	N
E/L	0.943	likely_pathogenic	0.9454	pathogenic	0.167	Stabilizing	0.968	D	0.654	neutral	None	None	None	None	N
E/M	0.9523	likely_pathogenic	0.9559	pathogenic	0.705	Stabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
E/N	0.8801	likely_pathogenic	0.8862	pathogenic	-1.26	Destabilizing	0.992	D	0.651	neutral	None	None	None	None	N
E/P	0.9818	likely_pathogenic	0.9811	pathogenic	-0.18	Destabilizing	0.992	D	0.747	deleterious	None	None	None	None	N
E/Q	0.6459	likely_pathogenic	0.6685	pathogenic	-1.094	Destabilizing	0.989	D	0.583	neutral	N	0.487422351	None	None	N
E/R	0.9209	likely_pathogenic	0.9285	pathogenic	-0.52	Destabilizing	0.983	D	0.645	neutral	None	None	None	None	N
E/S	0.8653	likely_pathogenic	0.8762	pathogenic	-1.634	Destabilizing	0.895	D	0.491	neutral	None	None	None	None	N
E/T	0.9276	likely_pathogenic	0.9321	pathogenic	-1.294	Destabilizing	0.983	D	0.657	neutral	None	None	None	None	N
E/V	0.8925	likely_pathogenic	0.9013	pathogenic	-0.18	Destabilizing	0.957	D	0.605	neutral	N	0.489387815	None	None	N
E/W	0.9956	likely_pathogenic	0.9955	pathogenic	-0.088	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.9833	likely_pathogenic	0.9841	pathogenic	-0.075	Destabilizing	0.997	D	0.73	prob.delet.	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.