TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18501	55726;55727;55728	chr2:178601496;178601495;178601494	chr2:179466223;179466222;179466221
N2AB	16860	50803;50804;50805	chr2:178601496;178601495;178601494	chr2:179466223;179466222;179466221
N2A	15933	48022;48023;48024	chr2:178601496;178601495;178601494	chr2:179466223;179466222;179466221
N2B	9436	28531;28532;28533	chr2:178601496;178601495;178601494	chr2:179466223;179466222;179466221
Novex-1	9561	28906;28907;28908	chr2:178601496;178601495;178601494	chr2:179466223;179466222;179466221
Novex-2	9628	29107;29108;29109	chr2:178601496;178601495;178601494	chr2:179466223;179466222;179466221
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-22
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.6402
• 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	None	None	1.0	N	0.701	0.263	0.201204373187	gnomAD-4.0.0	6.8453E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99807E-07	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	0.621	likely_pathogenic	0.6551	pathogenic	-0.182	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
K/C	0.8226	likely_pathogenic	0.8336	pathogenic	-0.169	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/D	0.7999	likely_pathogenic	0.8303	pathogenic	0.004	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/E	0.4709	ambiguous	0.4777	ambiguous	0.054	Stabilizing	0.999	D	0.599	neutral	N	0.442058246	None	None	N
K/F	0.9367	likely_pathogenic	0.9442	pathogenic	-0.052	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/G	0.6993	likely_pathogenic	0.7415	pathogenic	-0.479	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/H	0.4735	ambiguous	0.51	ambiguous	-0.814	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
K/I	0.6752	likely_pathogenic	0.697	pathogenic	0.55	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/L	0.6163	likely_pathogenic	0.6346	pathogenic	0.55	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/M	0.5096	ambiguous	0.5237	ambiguous	0.363	Stabilizing	1.0	D	0.743	deleterious	N	0.47325857	None	None	N
K/N	0.638	likely_pathogenic	0.6797	pathogenic	0.036	Stabilizing	1.0	D	0.701	prob.neutral	N	0.481136709	None	None	N
K/P	0.9794	likely_pathogenic	0.9855	pathogenic	0.336	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/Q	0.2155	likely_benign	0.2211	benign	-0.103	Destabilizing	1.0	D	0.679	prob.neutral	N	0.495066011	None	None	N
K/R	0.1034	likely_benign	0.1063	benign	-0.327	Destabilizing	0.999	D	0.549	neutral	N	0.497914315	None	None	N
K/S	0.6881	likely_pathogenic	0.7189	pathogenic	-0.5	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/T	0.4231	ambiguous	0.452	ambiguous	-0.277	Destabilizing	1.0	D	0.75	deleterious	N	0.474458666	None	None	N
K/V	0.5896	likely_pathogenic	0.6106	pathogenic	0.336	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/W	0.9312	likely_pathogenic	0.9383	pathogenic	0.009	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/Y	0.8663	likely_pathogenic	0.878	pathogenic	0.298	Stabilizing	1.0	D	0.767	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.