TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26834	80725;80726;80727	chr2:178565632;178565631;178565630	chr2:179430359;179430358;179430357
N2AB	25193	75802;75803;75804	chr2:178565632;178565631;178565630	chr2:179430359;179430358;179430357
N2A	24266	73021;73022;73023	chr2:178565632;178565631;178565630	chr2:179430359;179430358;179430357
N2B	17769	53530;53531;53532	chr2:178565632;178565631;178565630	chr2:179430359;179430358;179430357
Novex-1	17894	53905;53906;53907	chr2:178565632;178565631;178565630	chr2:179430359;179430358;179430357
Novex-2	17961	54106;54107;54108	chr2:178565632;178565631;178565630	chr2:179430359;179430358;179430357
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: Fn3-83
• Domain position: 55
• Structural Position: 83
• Q(SASA): 0.9276
• 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	0.992	N	0.627	0.402	0.289474373501	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
K/A	0.6921	likely_pathogenic	0.6235	pathogenic	0.025	Stabilizing	0.998	D	0.668	neutral	None	None	None	None	N
K/C	0.9147	likely_pathogenic	0.9018	pathogenic	-0.338	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/D	0.849	likely_pathogenic	0.8079	pathogenic	0.141	Stabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
K/E	0.6027	likely_pathogenic	0.5293	ambiguous	0.156	Stabilizing	0.992	D	0.627	neutral	N	0.494911296	None	None	N
K/F	0.9555	likely_pathogenic	0.9414	pathogenic	-0.162	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/G	0.7284	likely_pathogenic	0.6751	pathogenic	-0.169	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
K/H	0.5756	likely_pathogenic	0.5313	ambiguous	-0.336	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/I	0.7946	likely_pathogenic	0.7322	pathogenic	0.456	Stabilizing	0.977	D	0.687	prob.neutral	D	0.525735635	None	None	N
K/L	0.7384	likely_pathogenic	0.6874	pathogenic	0.456	Stabilizing	0.982	D	0.618	neutral	None	None	None	None	N
K/M	0.6541	likely_pathogenic	0.5794	pathogenic	0.111	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/N	0.7868	likely_pathogenic	0.7322	pathogenic	0.131	Stabilizing	0.999	D	0.735	prob.delet.	N	0.495450013	None	None	N
K/P	0.7755	likely_pathogenic	0.7531	pathogenic	0.34	Stabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
K/Q	0.3699	ambiguous	0.3163	benign	0.002	Stabilizing	0.994	D	0.718	prob.delet.	N	0.514171847	None	None	N
K/R	0.0856	likely_benign	0.0852	benign	-0.035	Destabilizing	0.987	D	0.579	neutral	N	0.451600449	None	None	N
K/S	0.76	likely_pathogenic	0.7023	pathogenic	-0.353	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
K/T	0.5012	ambiguous	0.4149	ambiguous	-0.189	Destabilizing	0.998	D	0.682	prob.neutral	N	0.484350372	None	None	N
K/V	0.7108	likely_pathogenic	0.6389	pathogenic	0.34	Stabilizing	0.987	D	0.655	neutral	None	None	None	None	N
K/W	0.9166	likely_pathogenic	0.9073	pathogenic	-0.196	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/Y	0.8875	likely_pathogenic	0.8598	pathogenic	0.158	Stabilizing	0.997	D	0.662	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.