TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23898	71917;71918;71919	chr2:178574440;178574439;178574438	chr2:179439167;179439166;179439165
N2AB	22257	66994;66995;66996	chr2:178574440;178574439;178574438	chr2:179439167;179439166;179439165
N2A	21330	64213;64214;64215	chr2:178574440;178574439;178574438	chr2:179439167;179439166;179439165
N2B	14833	44722;44723;44724	chr2:178574440;178574439;178574438	chr2:179439167;179439166;179439165
Novex-1	14958	45097;45098;45099	chr2:178574440;178574439;178574438	chr2:179439167;179439166;179439165
Novex-2	15025	45298;45299;45300	chr2:178574440;178574439;178574438	chr2:179439167;179439166;179439165
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-61
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1539
• 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/G	None	None	0.988	N	0.755	0.577	0.531922418639	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5712	likely_pathogenic	0.4899	ambiguous	-1.512	Destabilizing	0.958	D	0.677	prob.neutral	N	0.490197509	None	None	N
E/C	0.9345	likely_pathogenic	0.9297	pathogenic	-0.725	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/D	0.7369	likely_pathogenic	0.6757	pathogenic	-1.6	Destabilizing	0.958	D	0.587	neutral	N	0.484210028	None	None	N
E/F	0.969	likely_pathogenic	0.9565	pathogenic	-1.166	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/G	0.7773	likely_pathogenic	0.6941	pathogenic	-1.929	Destabilizing	0.988	D	0.755	deleterious	N	0.514088662	None	None	N
E/H	0.9233	likely_pathogenic	0.8964	pathogenic	-1.15	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/I	0.7816	likely_pathogenic	0.7079	pathogenic	-0.312	Destabilizing	0.995	D	0.869	deleterious	None	None	None	None	N
E/K	0.8064	likely_pathogenic	0.7187	pathogenic	-1.502	Destabilizing	0.919	D	0.603	neutral	N	0.467534124	None	None	N
E/L	0.8661	likely_pathogenic	0.8007	pathogenic	-0.312	Destabilizing	0.991	D	0.803	deleterious	None	None	None	None	N
E/M	0.8049	likely_pathogenic	0.751	pathogenic	0.464	Stabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
E/N	0.8831	likely_pathogenic	0.8328	pathogenic	-1.775	Destabilizing	0.991	D	0.723	prob.delet.	None	None	None	None	N
E/P	0.9988	likely_pathogenic	0.9979	pathogenic	-0.698	Destabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
E/Q	0.3399	likely_benign	0.2915	benign	-1.424	Destabilizing	0.414	N	0.394	neutral	N	0.475288172	None	None	N
E/R	0.8568	likely_pathogenic	0.7991	pathogenic	-1.391	Destabilizing	0.982	D	0.721	prob.delet.	None	None	None	None	N
E/S	0.6259	likely_pathogenic	0.5525	ambiguous	-2.439	Highly Destabilizing	0.968	D	0.631	neutral	None	None	None	None	N
E/T	0.6997	likely_pathogenic	0.6248	pathogenic	-2.039	Highly Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
E/V	0.6125	likely_pathogenic	0.5221	ambiguous	-0.698	Destabilizing	0.988	D	0.772	deleterious	N	0.474041811	None	None	N
E/W	0.9944	likely_pathogenic	0.9917	pathogenic	-1.26	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/Y	0.9525	likely_pathogenic	0.9371	pathogenic	-0.995	Destabilizing	0.998	D	0.823	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.