TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23337	70234;70235;70236	chr2:178576123;178576122;178576121	chr2:179440850;179440849;179440848
N2AB	21696	65311;65312;65313	chr2:178576123;178576122;178576121	chr2:179440850;179440849;179440848
N2A	20769	62530;62531;62532	chr2:178576123;178576122;178576121	chr2:179440850;179440849;179440848
N2B	14272	43039;43040;43041	chr2:178576123;178576122;178576121	chr2:179440850;179440849;179440848
Novex-1	14397	43414;43415;43416	chr2:178576123;178576122;178576121	chr2:179440850;179440849;179440848
Novex-2	14464	43615;43616;43617	chr2:178576123;178576122;178576121	chr2:179440850;179440849;179440848
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: Fn3-57
• Domain position: 98
• Structural Position: 131
• Q(SASA): 0.0492
• 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/K	None	None	0.001	N	0.215	0.146	0.252681307341	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	2.77824E-05	None	0	0	0	0	0
E/Q	rs1709996308	None	0.181	D	0.58	0.138	0.301122078929	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs1709996308	None	0.181	D	0.58	0.138	0.301122078929	gnomAD-4.0.0	2.56339E-06	None	None	None	None	N	None	1.69222E-05	0	None	0	0	None	0	0	2.39402E-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
E/A	0.4602	ambiguous	0.4654	ambiguous	-0.514	Destabilizing	0.1	N	0.6	neutral	N	0.502944494	None	None	N
E/C	0.9642	likely_pathogenic	0.9659	pathogenic	-0.107	Destabilizing	0.96	D	0.691	prob.delet.	None	None	None	None	N
E/D	0.1543	likely_benign	0.1391	benign	-0.424	Destabilizing	None	N	0.111	neutral	N	0.443010756	None	None	N
E/F	0.9664	likely_pathogenic	0.9691	pathogenic	-0.375	Destabilizing	0.864	D	0.699	prob.delet.	None	None	None	None	N
E/G	0.5012	ambiguous	0.5123	ambiguous	-0.721	Destabilizing	0.181	N	0.608	neutral	N	0.488121865	None	None	N
E/H	0.874	likely_pathogenic	0.883	pathogenic	-0.221	Destabilizing	0.676	D	0.565	neutral	None	None	None	None	N
E/I	0.876	likely_pathogenic	0.8759	pathogenic	0.001	Stabilizing	0.676	D	0.711	prob.delet.	None	None	None	None	N
E/K	0.6806	likely_pathogenic	0.7111	pathogenic	0.2	Stabilizing	0.001	N	0.215	neutral	N	0.519644743	None	None	N
E/L	0.8237	likely_pathogenic	0.8381	pathogenic	0.001	Stabilizing	0.507	D	0.657	prob.neutral	None	None	None	None	N
E/M	0.8772	likely_pathogenic	0.8863	pathogenic	0.156	Stabilizing	0.96	D	0.623	neutral	None	None	None	None	N
E/N	0.5715	likely_pathogenic	0.57	pathogenic	-0.139	Destabilizing	0.128	N	0.579	neutral	None	None	None	None	N
E/P	0.6937	likely_pathogenic	0.7172	pathogenic	-0.151	Destabilizing	0.676	D	0.66	prob.neutral	None	None	None	None	N
E/Q	0.4417	ambiguous	0.4776	ambiguous	-0.1	Destabilizing	0.181	N	0.58	neutral	D	0.527282791	None	None	N
E/R	0.7871	likely_pathogenic	0.8059	pathogenic	0.389	Stabilizing	0.128	N	0.61	neutral	None	None	None	None	N
E/S	0.5198	ambiguous	0.5346	ambiguous	-0.297	Destabilizing	0.128	N	0.51	neutral	None	None	None	None	N
E/T	0.7088	likely_pathogenic	0.7203	pathogenic	-0.127	Destabilizing	0.227	N	0.63	neutral	None	None	None	None	N
E/V	0.7104	likely_pathogenic	0.7111	pathogenic	-0.151	Destabilizing	0.437	N	0.619	neutral	N	0.506315026	None	None	N
E/W	0.9849	likely_pathogenic	0.9852	pathogenic	-0.204	Destabilizing	0.96	D	0.69	prob.delet.	None	None	None	None	N
E/Y	0.9234	likely_pathogenic	0.9278	pathogenic	-0.134	Destabilizing	0.864	D	0.66	prob.neutral	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.