TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18420	55483;55484;55485	chr2:178602013;178602012;178602011	chr2:179466740;179466739;179466738
N2AB	16779	50560;50561;50562	chr2:178602013;178602012;178602011	chr2:179466740;179466739;179466738
N2A	15852	47779;47780;47781	chr2:178602013;178602012;178602011	chr2:179466740;179466739;179466738
N2B	9355	28288;28289;28290	chr2:178602013;178602012;178602011	chr2:179466740;179466739;179466738
Novex-1	9480	28663;28664;28665	chr2:178602013;178602012;178602011	chr2:179466740;179466739;179466738
Novex-2	9547	28864;28865;28866	chr2:178602013;178602012;178602011	chr2:179466740;179466739;179466738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-115
• Domain position: 39
• Structural Position: 59
• Q(SASA): 0.6223
• 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	0.801	N	0.481	0.205	0.403328974453	gnomAD-4.0.0	4.10753E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39916E-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	0.3203	likely_benign	0.3452	ambiguous	-0.685	Destabilizing	0.525	D	0.418	neutral	None	None	None	None	N
K/C	0.6947	likely_pathogenic	0.6871	pathogenic	-0.636	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
K/D	0.5905	likely_pathogenic	0.6466	pathogenic	-0.194	Destabilizing	0.842	D	0.479	neutral	None	None	None	None	N
K/E	0.2623	likely_benign	0.2935	benign	-0.063	Destabilizing	0.801	D	0.481	neutral	N	0.472125729	None	None	N
K/F	0.7589	likely_pathogenic	0.7926	pathogenic	-0.278	Destabilizing	0.974	D	0.556	neutral	None	None	None	None	N
K/G	0.4021	ambiguous	0.4347	ambiguous	-1.076	Destabilizing	0.842	D	0.479	neutral	None	None	None	None	N
K/H	0.3723	ambiguous	0.3868	ambiguous	-1.389	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	N
K/I	0.3633	ambiguous	0.4086	ambiguous	0.34	Stabilizing	0.934	D	0.528	neutral	N	0.498640326	None	None	N
K/L	0.3312	likely_benign	0.3615	ambiguous	0.34	Stabilizing	0.728	D	0.493	neutral	None	None	None	None	N
K/M	0.2263	likely_benign	0.2474	benign	0.195	Stabilizing	0.991	D	0.507	neutral	None	None	None	None	N
K/N	0.3904	ambiguous	0.427	ambiguous	-0.589	Destabilizing	0.801	D	0.433	neutral	D	0.533827548	None	None	N
K/P	0.5415	ambiguous	0.5963	pathogenic	0.028	Stabilizing	0.974	D	0.497	neutral	None	None	None	None	N
K/Q	0.1821	likely_benign	0.1932	benign	-0.609	Destabilizing	0.966	D	0.512	neutral	N	0.491327565	None	None	N
K/R	0.0995	likely_benign	0.0966	benign	-0.695	Destabilizing	0.891	D	0.457	neutral	N	0.50471815	None	None	N
K/S	0.4175	ambiguous	0.446	ambiguous	-1.251	Destabilizing	0.172	N	0.189	neutral	None	None	None	None	N
K/T	0.1505	likely_benign	0.1601	benign	-0.903	Destabilizing	0.022	N	0.233	neutral	N	0.432068618	None	None	N
K/V	0.3117	likely_benign	0.3476	ambiguous	0.028	Stabilizing	0.728	D	0.481	neutral	None	None	None	None	N
K/W	0.8045	likely_pathogenic	0.8126	pathogenic	-0.155	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
K/Y	0.6447	likely_pathogenic	0.6761	pathogenic	0.123	Stabilizing	0.991	D	0.553	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.