TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26560	79903;79904;79905	chr2:178566454;178566453;178566452	chr2:179431181;179431180;179431179
N2AB	24919	74980;74981;74982	chr2:178566454;178566453;178566452	chr2:179431181;179431180;179431179
N2A	23992	72199;72200;72201	chr2:178566454;178566453;178566452	chr2:179431181;179431180;179431179
N2B	17495	52708;52709;52710	chr2:178566454;178566453;178566452	chr2:179431181;179431180;179431179
Novex-1	17620	53083;53084;53085	chr2:178566454;178566453;178566452	chr2:179431181;179431180;179431179
Novex-2	17687	53284;53285;53286	chr2:178566454;178566453;178566452	chr2:179431181;179431180;179431179
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-81
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.4087
• 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
K/E	rs994825543	None	0.885	N	0.662	0.249	0.272639205421	gnomAD-4.0.0	3.42168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59807E-06	0	1.65689E-05
K/T	None	None	0.982	N	0.679	0.375	0.353974658523	gnomAD-4.0.0	1.59196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
K/A	0.4146	ambiguous	0.3783	ambiguous	-1.279	Destabilizing	0.953	D	0.623	neutral	None	None	None	None	N
K/C	0.5664	likely_pathogenic	0.5344	ambiguous	-1.347	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.6501	likely_pathogenic	0.6053	pathogenic	-1.25	Destabilizing	0.986	D	0.693	prob.neutral	None	None	None	None	N
K/E	0.2127	likely_benign	0.203	benign	-1.022	Destabilizing	0.885	D	0.662	neutral	N	0.457544986	None	None	N
K/F	0.7387	likely_pathogenic	0.7113	pathogenic	-0.708	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
K/G	0.5838	likely_pathogenic	0.5379	ambiguous	-1.727	Destabilizing	0.953	D	0.675	neutral	None	None	None	None	N
K/H	0.2226	likely_benign	0.2152	benign	-1.904	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
K/I	0.3432	ambiguous	0.3217	benign	-0.042	Destabilizing	0.991	D	0.756	deleterious	N	0.501165264	None	None	N
K/L	0.3485	ambiguous	0.3233	benign	-0.042	Destabilizing	0.953	D	0.675	neutral	None	None	None	None	N
K/M	0.2178	likely_benign	0.2032	benign	-0.227	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
K/N	0.3474	ambiguous	0.3121	benign	-1.4	Destabilizing	0.982	D	0.657	neutral	N	0.461086724	None	None	N
K/P	0.9644	likely_pathogenic	0.9594	pathogenic	-0.43	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
K/Q	0.1062	likely_benign	0.1019	benign	-1.254	Destabilizing	0.322	N	0.445	neutral	N	0.443117038	None	None	N
K/R	0.0775	likely_benign	0.0746	benign	-0.972	Destabilizing	0.046	N	0.501	neutral	N	0.455854262	None	None	N
K/S	0.3816	ambiguous	0.3526	ambiguous	-2.045	Highly Destabilizing	0.953	D	0.619	neutral	None	None	None	None	N
K/T	0.1737	likely_benign	0.1581	benign	-1.572	Destabilizing	0.982	D	0.679	prob.neutral	N	0.456102191	None	None	N
K/V	0.3137	likely_benign	0.2941	benign	-0.43	Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.7332	likely_pathogenic	0.7114	pathogenic	-0.659	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
K/Y	0.5588	ambiguous	0.5428	ambiguous	-0.315	Destabilizing	0.998	D	0.735	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.