TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17869	53830;53831;53832	chr2:178605690;178605689;178605688	chr2:179470417;179470416;179470415
N2AB	16228	48907;48908;48909	chr2:178605690;178605689;178605688	chr2:179470417;179470416;179470415
N2A	15301	46126;46127;46128	chr2:178605690;178605689;178605688	chr2:179470417;179470416;179470415
N2B	8804	26635;26636;26637	chr2:178605690;178605689;178605688	chr2:179470417;179470416;179470415
Novex-1	8929	27010;27011;27012	chr2:178605690;178605689;178605688	chr2:179470417;179470416;179470415
Novex-2	8996	27211;27212;27213	chr2:178605690;178605689;178605688	chr2:179470417;179470416;179470415
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-18
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1786
• 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
L/R	None	None	0.995	D	0.779	0.579	0.85618202773	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
L/A	0.963	likely_pathogenic	0.9528	pathogenic	-2.393	Highly Destabilizing	0.959	D	0.71	prob.delet.	None	None	None	None	N
L/C	0.9121	likely_pathogenic	0.875	pathogenic	-1.858	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.999	pathogenic	-2.465	Highly Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
L/E	0.9952	likely_pathogenic	0.9955	pathogenic	-2.29	Highly Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
L/F	0.5346	ambiguous	0.3887	ambiguous	-1.485	Destabilizing	0.011	N	0.31	neutral	D	0.525474637	None	None	N
L/G	0.9904	likely_pathogenic	0.9893	pathogenic	-2.894	Highly Destabilizing	0.988	D	0.798	deleterious	None	None	None	None	N
L/H	0.9874	likely_pathogenic	0.9857	pathogenic	-2.316	Highly Destabilizing	0.999	D	0.795	deleterious	D	0.531496399	None	None	N
L/I	0.2693	likely_benign	0.2571	benign	-0.974	Destabilizing	0.811	D	0.703	prob.neutral	D	0.523338409	None	None	N
L/K	0.9906	likely_pathogenic	0.992	pathogenic	-1.758	Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
L/M	0.4063	ambiguous	0.3289	benign	-1.027	Destabilizing	0.988	D	0.71	prob.delet.	None	None	None	None	N
L/N	0.9909	likely_pathogenic	0.9912	pathogenic	-1.958	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
L/P	0.9536	likely_pathogenic	0.9304	pathogenic	-1.425	Destabilizing	0.995	D	0.812	deleterious	N	0.482473221	None	None	N
L/Q	0.9832	likely_pathogenic	0.9828	pathogenic	-1.902	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
L/R	0.9847	likely_pathogenic	0.9867	pathogenic	-1.439	Destabilizing	0.995	D	0.779	deleterious	D	0.531496399	None	None	N
L/S	0.9947	likely_pathogenic	0.9937	pathogenic	-2.673	Highly Destabilizing	0.988	D	0.772	deleterious	None	None	None	None	N
L/T	0.9663	likely_pathogenic	0.9646	pathogenic	-2.356	Highly Destabilizing	0.988	D	0.785	deleterious	None	None	None	None	N
L/V	0.3208	likely_benign	0.3178	benign	-1.425	Destabilizing	0.896	D	0.719	prob.delet.	N	0.498418535	None	None	N
L/W	0.9639	likely_pathogenic	0.9486	pathogenic	-1.789	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/Y	0.9608	likely_pathogenic	0.944	pathogenic	-1.502	Destabilizing	0.851	D	0.761	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.