TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17713	53362;53363;53364	chr2:178607551;178607550;178607549	chr2:179472278;179472277;179472276
N2AB	16072	48439;48440;48441	chr2:178607551;178607550;178607549	chr2:179472278;179472277;179472276
N2A	15145	45658;45659;45660	chr2:178607551;178607550;178607549	chr2:179472278;179472277;179472276
N2B	8648	26167;26168;26169	chr2:178607551;178607550;178607549	chr2:179472278;179472277;179472276
Novex-1	8773	26542;26543;26544	chr2:178607551;178607550;178607549	chr2:179472278;179472277;179472276
Novex-2	8840	26743;26744;26745	chr2:178607551;178607550;178607549	chr2:179472278;179472277;179472276
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-113
• Domain position: 37
• Structural Position: 58
• Q(SASA): 0.2202
• 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/V	rs1008171003	None	0.051	N	0.227	0.166	0.20549828249	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
L/V	rs1008171003	None	0.051	N	0.227	0.166	0.20549828249	gnomAD-4.0.0	2.56432E-06	None	None	None	None	N	None	0	1.69572E-05	None	0	0	None	0	0	0	0	2.84706E-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
L/A	0.4437	ambiguous	0.5494	ambiguous	-1.675	Destabilizing	0.688	D	0.455	neutral	None	None	None	None	N
L/C	0.7737	likely_pathogenic	0.8353	pathogenic	-1.177	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	N
L/D	0.8989	likely_pathogenic	0.9366	pathogenic	-0.908	Destabilizing	0.974	D	0.579	neutral	None	None	None	None	N
L/E	0.727	likely_pathogenic	0.8219	pathogenic	-0.865	Destabilizing	0.974	D	0.568	neutral	None	None	None	None	N
L/F	0.2869	likely_benign	0.2902	benign	-1.077	Destabilizing	0.949	D	0.511	neutral	None	None	None	None	N
L/G	0.805	likely_pathogenic	0.8767	pathogenic	-2.038	Highly Destabilizing	0.974	D	0.563	neutral	None	None	None	None	N
L/H	0.7091	likely_pathogenic	0.8115	pathogenic	-1.205	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
L/I	0.0956	likely_benign	0.0994	benign	-0.736	Destabilizing	0.016	N	0.369	neutral	None	None	None	None	N
L/K	0.7114	likely_pathogenic	0.8193	pathogenic	-1.169	Destabilizing	0.974	D	0.54	neutral	None	None	None	None	N
L/M	0.1628	likely_benign	0.1739	benign	-0.714	Destabilizing	0.934	D	0.54	neutral	N	0.507092025	None	None	N
L/N	0.7561	likely_pathogenic	0.8434	pathogenic	-1.042	Destabilizing	0.991	D	0.611	neutral	None	None	None	None	N
L/P	0.2944	likely_benign	0.3884	ambiguous	-1.019	Destabilizing	0.005	N	0.41	neutral	N	0.511556482	None	None	N
L/Q	0.6063	likely_pathogenic	0.7383	pathogenic	-1.124	Destabilizing	0.989	D	0.57	neutral	N	0.49653038	None	None	N
L/R	0.6641	likely_pathogenic	0.7742	pathogenic	-0.678	Destabilizing	0.989	D	0.569	neutral	N	0.504835266	None	None	N
L/S	0.72	likely_pathogenic	0.832	pathogenic	-1.712	Destabilizing	0.915	D	0.515	neutral	None	None	None	None	N
L/T	0.3871	ambiguous	0.5036	ambiguous	-1.53	Destabilizing	0.842	D	0.481	neutral	None	None	None	None	N
L/V	0.1342	likely_benign	0.1441	benign	-1.019	Destabilizing	0.051	N	0.227	neutral	N	0.453217468	None	None	N
L/W	0.5017	ambiguous	0.561	ambiguous	-1.142	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
L/Y	0.671	likely_pathogenic	0.7238	pathogenic	-0.926	Destabilizing	0.991	D	0.563	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.