TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14093	42502;42503;42504	chr2:178634504;178634503;178634502	chr2:179499231;179499230;179499229
N2AB	12452	37579;37580;37581	chr2:178634504;178634503;178634502	chr2:179499231;179499230;179499229
N2A	11525	34798;34799;34800	chr2:178634504;178634503;178634502	chr2:179499231;179499230;179499229
N2B	5028	15307;15308;15309	chr2:178634504;178634503;178634502	chr2:179499231;179499230;179499229
Novex-1	5153	15682;15683;15684	chr2:178634504;178634503;178634502	chr2:179499231;179499230;179499229
Novex-2	5220	15883;15884;15885	chr2:178634504;178634503;178634502	chr2:179499231;179499230;179499229
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-91
• Domain position: 40
• Structural Position: 59
• Q(SASA): 0.8327
• Predicted PPI site: I

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	rs2060181153	None	0.98	N	0.516	0.28	0.213573922156	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs2060181153	None	0.98	N	0.516	0.28	0.213573922156	gnomAD-4.0.0	6.84398E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99648E-07	0	0
K/R	rs1553743733	None	0.98	N	0.536	0.242	0.315903272564	gnomAD-4.0.0	1.5922E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86005E-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	0.449	ambiguous	0.4705	ambiguous	-0.064	Destabilizing	0.931	D	0.573	neutral	None	None	None	None	I
K/C	0.8398	likely_pathogenic	0.8189	pathogenic	-0.647	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	I
K/D	0.733	likely_pathogenic	0.7497	pathogenic	-0.163	Destabilizing	0.985	D	0.529	neutral	None	None	None	None	I
K/E	0.266	likely_benign	0.2925	benign	-0.155	Destabilizing	0.98	D	0.587	neutral	N	0.457408525	None	None	I
K/F	0.8639	likely_pathogenic	0.864	pathogenic	-0.4	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	I
K/G	0.5997	likely_pathogenic	0.6234	pathogenic	-0.201	Destabilizing	0.985	D	0.551	neutral	None	None	None	None	I
K/H	0.3876	ambiguous	0.3718	ambiguous	-0.257	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	I
K/I	0.5197	ambiguous	0.5388	ambiguous	0.215	Stabilizing	0.991	D	0.61	neutral	None	None	None	None	I
K/L	0.5006	ambiguous	0.5005	ambiguous	0.215	Stabilizing	0.97	D	0.562	neutral	None	None	None	None	I
K/M	0.3952	ambiguous	0.4044	ambiguous	-0.235	Destabilizing	1.0	D	0.547	neutral	D	0.606095449	None	None	I
K/N	0.5328	ambiguous	0.5632	ambiguous	-0.232	Destabilizing	0.98	D	0.516	neutral	N	0.508426336	None	None	I
K/P	0.6721	likely_pathogenic	0.6823	pathogenic	0.145	Stabilizing	0.999	D	0.503	neutral	None	None	None	None	I
K/Q	0.1635	likely_benign	0.1633	benign	-0.295	Destabilizing	0.998	D	0.516	neutral	N	0.496696274	None	None	I
K/R	0.1065	likely_benign	0.1058	benign	-0.167	Destabilizing	0.98	D	0.536	neutral	N	0.492105614	None	None	I
K/S	0.5065	ambiguous	0.526	ambiguous	-0.6	Destabilizing	0.871	D	0.567	neutral	None	None	None	None	I
K/T	0.2012	likely_benign	0.2094	benign	-0.462	Destabilizing	0.122	N	0.319	neutral	N	0.424245405	None	None	I
K/V	0.4861	ambiguous	0.4926	ambiguous	0.145	Stabilizing	0.97	D	0.555	neutral	None	None	None	None	I
K/W	0.8925	likely_pathogenic	0.8911	pathogenic	-0.522	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
K/Y	0.7767	likely_pathogenic	0.7679	pathogenic	-0.162	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	I

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.