TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2452	7579;7580;7581	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427
N2AB	2452	7579;7580;7581	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427
N2A	2452	7579;7580;7581	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427
N2B	2406	7441;7442;7443	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427
Novex-1	2406	7441;7442;7443	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427
Novex-2	2406	7441;7442;7443	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427
Novex-3	2452	7579;7580;7581	chr2:178773702;178773701;178773700	chr2:179638429;179638428;179638427

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-14
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7581
• 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	None	None	0.008	N	0.233	0.286	0.300110245524	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.3273	likely_benign	0.323	benign	-0.016	Destabilizing	0.633	D	0.581	neutral	None	None	None	None	N
K/C	0.6918	likely_pathogenic	0.6851	pathogenic	-0.109	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
K/D	0.5109	ambiguous	0.5015	ambiguous	-0.058	Destabilizing	0.633	D	0.589	neutral	None	None	None	None	N
K/E	0.1263	likely_benign	0.1288	benign	-0.026	Destabilizing	0.008	N	0.233	neutral	N	0.516110765	None	None	N
K/F	0.8023	likely_pathogenic	0.7907	pathogenic	-0.024	Destabilizing	0.987	D	0.667	neutral	None	None	None	None	N
K/G	0.4367	ambiguous	0.4265	ambiguous	-0.269	Destabilizing	0.775	D	0.545	neutral	None	None	None	None	N
K/H	0.2954	likely_benign	0.292	benign	-0.592	Destabilizing	0.989	D	0.636	neutral	None	None	None	None	N
K/I	0.4175	ambiguous	0.4095	ambiguous	0.589	Stabilizing	0.949	D	0.678	prob.neutral	D	0.619885244	None	None	N
K/L	0.3931	ambiguous	0.3879	ambiguous	0.589	Stabilizing	0.775	D	0.553	neutral	None	None	None	None	N
K/M	0.2695	likely_benign	0.2684	benign	0.298	Stabilizing	0.989	D	0.629	neutral	None	None	None	None	N
K/N	0.3506	ambiguous	0.3411	ambiguous	0.137	Stabilizing	0.901	D	0.575	neutral	D	0.546337417	None	None	N
K/P	0.7669	likely_pathogenic	0.7657	pathogenic	0.416	Stabilizing	0.961	D	0.643	neutral	None	None	None	None	N
K/Q	0.1199	likely_benign	0.1197	benign	0.008	Stabilizing	0.034	N	0.181	neutral	N	0.507369616	None	None	N
K/R	0.0885	likely_benign	0.0888	benign	-0.221	Destabilizing	0.565	D	0.545	neutral	N	0.509034581	None	None	N
K/S	0.3478	ambiguous	0.3424	ambiguous	-0.303	Destabilizing	0.633	D	0.539	neutral	None	None	None	None	N
K/T	0.1622	likely_benign	0.163	benign	-0.114	Destabilizing	0.901	D	0.589	neutral	N	0.514566209	None	None	N
K/V	0.3612	ambiguous	0.3559	ambiguous	0.416	Stabilizing	0.923	D	0.561	neutral	None	None	None	None	N
K/W	0.7808	likely_pathogenic	0.7736	pathogenic	-0.036	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.6692	likely_pathogenic	0.658	pathogenic	0.278	Stabilizing	0.961	D	0.674	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.