TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3020	9283;9284;9285	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503
N2AB	3020	9283;9284;9285	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503
N2A	3020	9283;9284;9285	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503
N2B	2974	9145;9146;9147	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503
Novex-1	2974	9145;9146;9147	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503
Novex-2	2974	9145;9146;9147	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503
Novex-3	3020	9283;9284;9285	chr2:178768778;178768777;178768776	chr2:179633505;179633504;179633503

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-20
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.4183
• 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/N	rs2090976989	None	0.801	N	0.331	0.16	0.110078149338	gnomAD-4.0.0	1.5906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0217E-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	0.4033	ambiguous	0.5484	ambiguous	0.076	Stabilizing	0.688	D	0.351	neutral	None	None	None	None	N
K/C	0.792	likely_pathogenic	0.8844	pathogenic	-0.255	Destabilizing	0.998	D	0.335	neutral	None	None	None	None	N
K/D	0.5229	ambiguous	0.6632	pathogenic	-0.091	Destabilizing	0.842	D	0.357	neutral	None	None	None	None	N
K/E	0.2808	likely_benign	0.4236	ambiguous	-0.08	Destabilizing	0.454	N	0.349	neutral	N	0.420710628	None	None	N
K/F	0.8226	likely_pathogenic	0.9051	pathogenic	-0.133	Destabilizing	0.991	D	0.311	neutral	None	None	None	None	N
K/G	0.3492	ambiguous	0.4448	ambiguous	-0.111	Destabilizing	0.842	D	0.375	neutral	None	None	None	None	N
K/H	0.3397	likely_benign	0.4405	ambiguous	-0.299	Destabilizing	0.974	D	0.299	neutral	None	None	None	None	N
K/I	0.6041	likely_pathogenic	0.7488	pathogenic	0.491	Stabilizing	0.949	D	0.344	neutral	None	None	None	None	N
K/L	0.4427	ambiguous	0.5895	pathogenic	0.491	Stabilizing	0.842	D	0.385	neutral	None	None	None	None	N
K/M	0.2987	likely_benign	0.4293	ambiguous	0.088	Stabilizing	0.989	D	0.299	neutral	N	0.454089933	None	None	N
K/N	0.275	likely_benign	0.4263	ambiguous	0.157	Stabilizing	0.801	D	0.331	neutral	N	0.437255587	None	None	N
K/P	0.7284	likely_pathogenic	0.8022	pathogenic	0.38	Stabilizing	0.974	D	0.317	neutral	None	None	None	None	N
K/Q	0.1498	likely_benign	0.2052	benign	0.034	Stabilizing	0.022	N	0.141	neutral	N	0.380886774	None	None	N
K/R	0.1102	likely_benign	0.1238	benign	-0.044	Destabilizing	0.669	D	0.295	neutral	N	0.403091636	None	None	N
K/S	0.4001	ambiguous	0.5608	ambiguous	-0.238	Destabilizing	0.525	D	0.291	neutral	None	None	None	None	N
K/T	0.2779	likely_benign	0.4089	ambiguous	-0.087	Destabilizing	0.051	N	0.228	neutral	N	0.43690837	None	None	N
K/V	0.5626	ambiguous	0.7035	pathogenic	0.38	Stabilizing	0.842	D	0.409	neutral	None	None	None	None	N
K/W	0.8421	likely_pathogenic	0.909	pathogenic	-0.213	Destabilizing	0.998	D	0.362	neutral	None	None	None	None	N
K/Y	0.6114	likely_pathogenic	0.7407	pathogenic	0.141	Stabilizing	0.991	D	0.32	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.