TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9339	28240;28241;28242	chr2:178711221;178711220;178711219	chr2:179575948;179575947;179575946
N2AB	9022	27289;27290;27291	chr2:178711221;178711220;178711219	chr2:179575948;179575947;179575946
N2A	8095	24508;24509;24510	chr2:178711221;178711220;178711219	chr2:179575948;179575947;179575946
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-79
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.7001
• 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/R	rs878989601	None	None	None	0.237	0.093	0.104622674875	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs878989601	None	None	None	0.237	0.093	0.104622674875	gnomAD-4.0.0	6.57117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	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	0.1944	likely_benign	0.2347	benign	0.03	Stabilizing	None	N	0.189	neutral	None	None	None	None	N
K/C	0.5128	ambiguous	0.5209	ambiguous	-0.256	Destabilizing	0.676	D	0.255	neutral	None	None	None	None	N
K/D	0.3312	likely_benign	0.3837	ambiguous	None	Stabilizing	None	N	0.263	neutral	None	None	None	None	N
K/E	0.0997	likely_benign	0.1318	benign	0.02	Stabilizing	None	N	0.208	neutral	None	None	None	None	N
K/F	0.3455	ambiguous	0.3626	ambiguous	-0.141	Destabilizing	0.356	N	0.279	neutral	None	None	None	None	N
K/G	0.3297	likely_benign	0.364	ambiguous	-0.174	Destabilizing	0.016	N	0.356	neutral	None	None	None	None	N
K/H	0.1679	likely_benign	0.1789	benign	-0.371	Destabilizing	0.214	N	0.303	neutral	None	None	None	None	N
K/I	0.0964	likely_benign	0.1211	benign	0.491	Stabilizing	0.038	N	0.368	neutral	None	None	None	None	N
K/L	0.1337	likely_benign	0.1585	benign	0.491	Stabilizing	0.016	N	0.348	neutral	None	None	None	None	N
K/M	0.0942	likely_benign	0.1265	benign	0.105	Stabilizing	0.295	N	0.303	neutral	None	None	None	None	N
K/N	0.1707	likely_benign	0.1978	benign	0.142	Stabilizing	0.055	N	0.289	neutral	None	None	None	None	N
K/P	0.8523	likely_pathogenic	0.9015	pathogenic	0.365	Stabilizing	0.136	N	0.376	neutral	None	None	None	None	N
K/Q	0.0813	likely_benign	0.1018	benign	0.032	Stabilizing	0.001	N	0.227	neutral	None	None	None	None	N
K/R	0.0813	likely_benign	0.0906	benign	-0.061	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
K/S	0.197	likely_benign	0.2178	benign	-0.288	Destabilizing	0.016	N	0.283	neutral	None	None	None	None	N
K/T	0.1006	likely_benign	0.132	benign	-0.119	Destabilizing	0.055	N	0.344	neutral	None	None	None	None	N
K/V	0.1084	likely_benign	0.1462	benign	0.365	Stabilizing	None	N	0.176	neutral	None	None	None	None	N
K/W	0.5536	ambiguous	0.5691	pathogenic	-0.204	Destabilizing	0.864	D	0.267	neutral	None	None	None	None	N
K/Y	0.3093	likely_benign	0.3233	benign	0.147	Stabilizing	0.356	N	0.287	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.