TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29644	89155;89156;89157	chr2:178554181;178554180;178554179	chr2:179418908;179418907;179418906
N2AB	28003	84232;84233;84234	chr2:178554181;178554180;178554179	chr2:179418908;179418907;179418906
N2A	27076	81451;81452;81453	chr2:178554181;178554180;178554179	chr2:179418908;179418907;179418906
N2B	20579	61960;61961;61962	chr2:178554181;178554180;178554179	chr2:179418908;179418907;179418906
Novex-1	20704	62335;62336;62337	chr2:178554181;178554180;178554179	chr2:179418908;179418907;179418906
Novex-2	20771	62536;62537;62538	chr2:178554181;178554180;178554179	chr2:179418908;179418907;179418906
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: Fn3-104
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4102
• 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	None	None	0.27	N	0.243	0.059	0.201204373187	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	0.3392	likely_benign	0.3737	ambiguous	0.029	Stabilizing	0.495	N	0.341	neutral	None	None	None	None	N
K/C	0.6259	likely_pathogenic	0.6292	pathogenic	-0.189	Destabilizing	0.995	D	0.371	neutral	None	None	None	None	N
K/D	0.5857	likely_pathogenic	0.6381	pathogenic	0.191	Stabilizing	0.704	D	0.324	neutral	None	None	None	None	N
K/E	0.2959	likely_benign	0.3587	ambiguous	0.205	Stabilizing	0.27	N	0.315	neutral	N	0.4034225	None	None	N
K/F	0.8265	likely_pathogenic	0.8534	pathogenic	-0.154	Destabilizing	0.893	D	0.41	neutral	None	None	None	None	N
K/G	0.4183	ambiguous	0.4668	ambiguous	-0.181	Destabilizing	0.704	D	0.363	neutral	None	None	None	None	N
K/H	0.2934	likely_benign	0.3162	benign	-0.447	Destabilizing	0.944	D	0.363	neutral	None	None	None	None	N
K/I	0.5726	likely_pathogenic	0.6062	pathogenic	0.503	Stabilizing	0.543	D	0.415	neutral	None	None	None	None	N
K/L	0.4322	ambiguous	0.4433	ambiguous	0.503	Stabilizing	0.069	N	0.286	neutral	None	None	None	None	N
K/M	0.2449	likely_benign	0.2564	benign	0.28	Stabilizing	0.029	N	0.083	neutral	N	0.460318719	None	None	N
K/N	0.4175	ambiguous	0.4532	ambiguous	0.246	Stabilizing	0.642	D	0.305	neutral	N	0.382932584	None	None	N
K/P	0.9359	likely_pathogenic	0.9521	pathogenic	0.373	Stabilizing	0.828	D	0.377	neutral	None	None	None	None	N
K/Q	0.1556	likely_benign	0.1822	benign	0.087	Stabilizing	0.023	N	0.083	neutral	N	0.447157421	None	None	N
K/R	0.0885	likely_benign	0.0952	benign	-0.009	Destabilizing	0.27	N	0.243	neutral	N	0.464761747	None	None	N
K/S	0.4056	ambiguous	0.4508	ambiguous	-0.269	Destabilizing	0.495	N	0.255	neutral	None	None	None	None	N
K/T	0.2408	likely_benign	0.285	benign	-0.101	Destabilizing	0.642	D	0.321	neutral	N	0.454526111	None	None	N
K/V	0.4006	ambiguous	0.4178	ambiguous	0.373	Stabilizing	0.329	N	0.343	neutral	None	None	None	None	N
K/W	0.7986	likely_pathogenic	0.8375	pathogenic	-0.164	Destabilizing	0.995	D	0.375	neutral	None	None	None	None	N
K/Y	0.6279	likely_pathogenic	0.6684	pathogenic	0.196	Stabilizing	0.944	D	0.389	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.