TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27975	84148;84149;84150	chr2:178562209;178562208;178562207	chr2:179426936;179426935;179426934
N2AB	26334	79225;79226;79227	chr2:178562209;178562208;178562207	chr2:179426936;179426935;179426934
N2A	25407	76444;76445;76446	chr2:178562209;178562208;178562207	chr2:179426936;179426935;179426934
N2B	18910	56953;56954;56955	chr2:178562209;178562208;178562207	chr2:179426936;179426935;179426934
Novex-1	19035	57328;57329;57330	chr2:178562209;178562208;178562207	chr2:179426936;179426935;179426934
Novex-2	19102	57529;57530;57531	chr2:178562209;178562208;178562207	chr2:179426936;179426935;179426934
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: Ig-142
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5577
• 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	0.942	N	0.529	0.328	0.293502639404	gnomAD-4.0.0	6.8473E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99777E-07	0	0
K/R	None	None	0.698	N	0.566	0.176	0.264081493735	gnomAD-4.0.0	1.5944E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86174E-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	0.5984	likely_pathogenic	0.5251	ambiguous	-0.123	Destabilizing	0.754	D	0.594	neutral	None	None	None	None	N
K/C	0.8604	likely_pathogenic	0.7981	pathogenic	-0.36	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
K/D	0.8899	likely_pathogenic	0.863	pathogenic	-0.025	Destabilizing	0.956	D	0.564	neutral	None	None	None	None	N
K/E	0.4349	ambiguous	0.3919	ambiguous	0.026	Stabilizing	0.698	D	0.581	neutral	N	0.485794915	None	None	N
K/F	0.8924	likely_pathogenic	0.8432	pathogenic	-0.063	Destabilizing	0.993	D	0.687	prob.neutral	None	None	None	None	N
K/G	0.774	likely_pathogenic	0.7186	pathogenic	-0.396	Destabilizing	0.019	N	0.453	neutral	None	None	None	None	N
K/H	0.5173	ambiguous	0.4376	ambiguous	-0.622	Destabilizing	0.994	D	0.585	neutral	None	None	None	None	N
K/I	0.5478	ambiguous	0.4746	ambiguous	0.539	Stabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	N
K/L	0.4933	ambiguous	0.4043	ambiguous	0.539	Stabilizing	0.956	D	0.591	neutral	None	None	None	None	N
K/M	0.386	ambiguous	0.341	ambiguous	0.19	Stabilizing	0.997	D	0.586	neutral	N	0.485189485	None	None	N
K/N	0.7612	likely_pathogenic	0.7135	pathogenic	-0.125	Destabilizing	0.942	D	0.529	neutral	N	0.486555384	None	None	N
K/P	0.7024	likely_pathogenic	0.6211	pathogenic	0.348	Stabilizing	0.978	D	0.598	neutral	None	None	None	None	N
K/Q	0.2294	likely_benign	0.1978	benign	-0.218	Destabilizing	0.125	N	0.295	neutral	N	0.466757194	None	None	N
K/R	0.0939	likely_benign	0.0858	benign	-0.303	Destabilizing	0.698	D	0.566	neutral	N	0.463871605	None	None	N
K/S	0.7663	likely_pathogenic	0.7079	pathogenic	-0.619	Destabilizing	0.86	D	0.578	neutral	None	None	None	None	N
K/T	0.4084	ambiguous	0.3715	ambiguous	-0.397	Destabilizing	0.942	D	0.547	neutral	D	0.523477269	None	None	N
K/V	0.5127	ambiguous	0.4405	ambiguous	0.348	Stabilizing	0.978	D	0.624	neutral	None	None	None	None	N
K/W	0.8951	likely_pathogenic	0.848	pathogenic	-0.053	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
K/Y	0.8206	likely_pathogenic	0.7626	pathogenic	0.259	Stabilizing	0.993	D	0.668	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.