TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24733	74422;74423;74424	chr2:178571935;178571934;178571933	chr2:179436662;179436661;179436660
N2AB	23092	69499;69500;69501	chr2:178571935;178571934;178571933	chr2:179436662;179436661;179436660
N2A	22165	66718;66719;66720	chr2:178571935;178571934;178571933	chr2:179436662;179436661;179436660
N2B	15668	47227;47228;47229	chr2:178571935;178571934;178571933	chr2:179436662;179436661;179436660
Novex-1	15793	47602;47603;47604	chr2:178571935;178571934;178571933	chr2:179436662;179436661;179436660
Novex-2	15860	47803;47804;47805	chr2:178571935;178571934;178571933	chr2:179436662;179436661;179436660
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-133
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1378
• 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/Q	None	None	0.999	N	0.889	0.482	0.811399548127	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.91	likely_pathogenic	0.9155	pathogenic	-2.253	Highly Destabilizing	0.968	D	0.693	prob.neutral	None	None	None	None	N
L/C	0.8362	likely_pathogenic	0.8371	pathogenic	-1.636	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/D	0.9987	likely_pathogenic	0.999	pathogenic	-1.755	Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
L/E	0.991	likely_pathogenic	0.9923	pathogenic	-1.639	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
L/F	0.5169	ambiguous	0.5174	ambiguous	-1.384	Destabilizing	0.991	D	0.789	deleterious	None	None	None	None	N
L/G	0.9852	likely_pathogenic	0.9873	pathogenic	-2.713	Highly Destabilizing	0.995	D	0.87	deleterious	None	None	None	None	N
L/H	0.9739	likely_pathogenic	0.9777	pathogenic	-1.885	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/I	0.1571	likely_benign	0.1575	benign	-0.989	Destabilizing	0.142	N	0.319	neutral	N	0.466060108	None	None	N
L/K	0.9758	likely_pathogenic	0.9801	pathogenic	-1.714	Destabilizing	0.995	D	0.863	deleterious	None	None	None	None	N
L/M	0.2398	likely_benign	0.2446	benign	-0.873	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
L/N	0.9923	likely_pathogenic	0.9935	pathogenic	-1.733	Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
L/P	0.9965	likely_pathogenic	0.9974	pathogenic	-1.383	Destabilizing	0.998	D	0.89	deleterious	N	0.515377385	None	None	N
L/Q	0.9545	likely_pathogenic	0.961	pathogenic	-1.757	Destabilizing	0.999	D	0.889	deleterious	N	0.515377385	None	None	N
L/R	0.9572	likely_pathogenic	0.9641	pathogenic	-1.215	Destabilizing	0.998	D	0.887	deleterious	N	0.49701964	None	None	N
L/S	0.9836	likely_pathogenic	0.9857	pathogenic	-2.497	Highly Destabilizing	0.995	D	0.867	deleterious	None	None	None	None	N
L/T	0.9164	likely_pathogenic	0.9247	pathogenic	-2.239	Highly Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
L/V	0.186	likely_benign	0.1835	benign	-1.383	Destabilizing	0.618	D	0.559	neutral	N	0.457301765	None	None	N
L/W	0.9168	likely_pathogenic	0.9261	pathogenic	-1.546	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/Y	0.94	likely_pathogenic	0.9455	pathogenic	-1.323	Destabilizing	0.995	D	0.876	deleterious	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.