TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9931	30016;30017;30018	chr2:178704681;178704680;178704679	chr2:179569408;179569407;179569406
N2AB	9614	29065;29066;29067	chr2:178704681;178704680;178704679	chr2:179569408;179569407;179569406
N2A	8687	26284;26285;26286	chr2:178704681;178704680;178704679	chr2:179569408;179569407;179569406
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-84
• Domain position: 32
• Structural Position: 45
• Q(SASA): 0.2806
• Predicted PPI site: I

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/N	None	None	0.801	None	0.502	0.182	0.136095386433	gnomAD-4.0.0	1.59616E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86561E-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
K/A	0.7223	likely_pathogenic	0.7281	pathogenic	-0.003	Destabilizing	0.029	N	0.229	neutral	None	None	None	None	I
K/C	0.9334	likely_pathogenic	0.9435	pathogenic	-0.489	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	I
K/D	0.8982	likely_pathogenic	0.9047	pathogenic	-0.204	Destabilizing	0.842	D	0.527	neutral	None	None	None	None	I
K/E	0.5757	likely_pathogenic	0.5458	ambiguous	-0.215	Destabilizing	0.454	N	0.482	neutral	None	None	None	None	I
K/F	0.9695	likely_pathogenic	0.9717	pathogenic	-0.34	Destabilizing	0.991	D	0.599	neutral	None	None	None	None	I
K/G	0.8756	likely_pathogenic	0.8776	pathogenic	-0.136	Destabilizing	0.842	D	0.555	neutral	None	None	None	None	I
K/H	0.5947	likely_pathogenic	0.6305	pathogenic	-0.248	Destabilizing	0.974	D	0.561	neutral	None	None	None	None	I
K/I	0.7357	likely_pathogenic	0.7276	pathogenic	0.259	Stabilizing	0.949	D	0.609	neutral	None	None	None	None	I
K/L	0.7318	likely_pathogenic	0.7405	pathogenic	0.259	Stabilizing	0.842	D	0.557	neutral	None	None	None	None	I
K/M	0.639	likely_pathogenic	0.6041	pathogenic	-0.063	Destabilizing	0.966	D	0.567	neutral	None	None	None	None	I
K/N	0.7474	likely_pathogenic	0.782	pathogenic	-0.047	Destabilizing	0.801	D	0.502	neutral	None	None	None	None	I
K/P	0.8612	likely_pathogenic	0.8734	pathogenic	0.196	Stabilizing	0.915	D	0.579	neutral	None	None	None	None	I
K/Q	0.2914	likely_benign	0.309	benign	-0.187	Destabilizing	0.051	N	0.251	neutral	None	None	None	None	I
K/R	0.1458	likely_benign	0.152	benign	-0.123	Destabilizing	0.669	D	0.44	neutral	None	None	None	None	I
K/S	0.7362	likely_pathogenic	0.7683	pathogenic	-0.436	Destabilizing	0.525	D	0.468	neutral	None	None	None	None	I
K/T	0.3704	ambiguous	0.3723	ambiguous	-0.325	Destabilizing	0.022	N	0.22	neutral	None	None	None	None	I
K/V	0.6761	likely_pathogenic	0.6915	pathogenic	0.196	Stabilizing	0.842	D	0.549	neutral	None	None	None	None	I
K/W	0.9775	likely_pathogenic	0.9756	pathogenic	-0.429	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	I
K/Y	0.9396	likely_pathogenic	0.9354	pathogenic	-0.071	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	I

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.