TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7477	22654;22655;22656	chr2:178722358;178722357;178722356	chr2:179587085;179587084;179587083
N2AB	7160	21703;21704;21705	chr2:178722358;178722357;178722356	chr2:179587085;179587084;179587083
N2A	6233	18922;18923;18924	chr2:178722358;178722357;178722356	chr2:179587085;179587084;179587083
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-59
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.4443
• 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/T	rs774575742	-1.089	0.01	N	0.29	0.275	0.264081493735	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	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
K/A	0.3438	ambiguous	0.4041	ambiguous	-0.906	Destabilizing	0.3	N	0.382	neutral	None	None	None	None	N
K/C	0.6781	likely_pathogenic	0.7149	pathogenic	-1.14	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	N
K/D	0.5152	ambiguous	0.5814	pathogenic	-0.544	Destabilizing	0.329	N	0.425	neutral	None	None	None	None	N
K/E	0.1289	likely_benign	0.1532	benign	-0.37	Destabilizing	0.01	N	0.303	neutral	N	0.421888909	None	None	N
K/F	0.7247	likely_pathogenic	0.7722	pathogenic	-0.424	Destabilizing	0.944	D	0.528	neutral	None	None	None	None	N
K/G	0.5205	ambiguous	0.5865	pathogenic	-1.317	Destabilizing	0.495	N	0.449	neutral	None	None	None	None	N
K/H	0.1848	likely_benign	0.2262	benign	-1.54	Destabilizing	0.007	N	0.39	neutral	None	None	None	None	N
K/I	0.3032	likely_benign	0.3442	ambiguous	0.192	Stabilizing	0.642	D	0.561	neutral	N	0.465890403	None	None	N
K/L	0.3104	likely_benign	0.3574	ambiguous	0.192	Stabilizing	0.495	N	0.471	neutral	None	None	None	None	N
K/M	0.1914	likely_benign	0.2107	benign	-0.072	Destabilizing	0.944	D	0.486	neutral	None	None	None	None	N
K/N	0.2669	likely_benign	0.3214	benign	-0.957	Destabilizing	0.01	N	0.294	neutral	N	0.45057702	None	None	N
K/P	0.9501	likely_pathogenic	0.963	pathogenic	-0.146	Destabilizing	0.828	D	0.485	neutral	None	None	None	None	N
K/Q	0.0817	likely_benign	0.0916	benign	-0.936	Destabilizing	0.01	N	0.304	neutral	N	0.411346629	None	None	N
K/R	0.0749	likely_benign	0.0812	benign	-0.815	Destabilizing	0.002	N	0.275	neutral	N	0.428852167	None	None	N
K/S	0.3002	likely_benign	0.3671	ambiguous	-1.657	Destabilizing	0.329	N	0.398	neutral	None	None	None	None	N
K/T	0.1158	likely_benign	0.1393	benign	-1.256	Destabilizing	0.01	N	0.29	neutral	N	0.434911348	None	None	N
K/V	0.2957	likely_benign	0.3384	benign	-0.146	Destabilizing	0.704	D	0.531	neutral	None	None	None	None	N
K/W	0.6827	likely_pathogenic	0.7496	pathogenic	-0.296	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
K/Y	0.5218	ambiguous	0.5828	pathogenic	0.024	Stabilizing	0.893	D	0.581	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.