TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29047	87364;87365;87366	chr2:178558215;178558214;178558213	chr2:179422942;179422941;179422940
N2AB	27406	82441;82442;82443	chr2:178558215;178558214;178558213	chr2:179422942;179422941;179422940
N2A	26479	79660;79661;79662	chr2:178558215;178558214;178558213	chr2:179422942;179422941;179422940
N2B	19982	60169;60170;60171	chr2:178558215;178558214;178558213	chr2:179422942;179422941;179422940
Novex-1	20107	60544;60545;60546	chr2:178558215;178558214;178558213	chr2:179422942;179422941;179422940
Novex-2	20174	60745;60746;60747	chr2:178558215;178558214;178558213	chr2:179422942;179422941;179422940
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-145
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1269
• 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	rs1702242034	None	0.864	N	0.534	0.196	0.225215365344	gnomAD-4.0.0	1.60761E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86852E-06	0	0
K/R	None	None	0.013	N	0.322	0.087	0.32714864917	gnomAD-4.0.0	1.56044E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.70627E-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	0.2315	likely_benign	0.2647	benign	0.076	Stabilizing	0.547	D	0.498	neutral	None	None	None	None	N
K/C	0.6523	likely_pathogenic	0.6261	pathogenic	-0.154	Destabilizing	0.985	D	0.678	prob.neutral	None	None	None	None	N
K/D	0.4626	ambiguous	0.4852	ambiguous	-0.083	Destabilizing	0.894	D	0.57	neutral	None	None	None	None	N
K/E	0.1487	likely_benign	0.1578	benign	-0.074	Destabilizing	0.645	D	0.507	neutral	N	0.468042486	None	None	N
K/F	0.7845	likely_pathogenic	0.791	pathogenic	-0.129	Destabilizing	0.945	D	0.677	prob.neutral	None	None	None	None	N
K/G	0.3079	likely_benign	0.3158	benign	-0.112	Destabilizing	0.707	D	0.559	neutral	None	None	None	None	N
K/H	0.2883	likely_benign	0.2816	benign	-0.308	Destabilizing	0.995	D	0.591	neutral	None	None	None	None	N
K/I	0.3846	ambiguous	0.4166	ambiguous	0.495	Stabilizing	0.809	D	0.672	neutral	None	None	None	None	N
K/L	0.3371	likely_benign	0.3682	ambiguous	0.495	Stabilizing	0.547	D	0.542	neutral	None	None	None	None	N
K/M	0.2215	likely_benign	0.2535	benign	0.133	Stabilizing	0.98	D	0.595	neutral	N	0.488361831	None	None	N
K/N	0.2662	likely_benign	0.3064	benign	0.255	Stabilizing	0.864	D	0.534	neutral	N	0.487495039	None	None	N
K/P	0.7995	likely_pathogenic	0.8243	pathogenic	0.382	Stabilizing	0.945	D	0.613	neutral	None	None	None	None	N
K/Q	0.1086	likely_benign	0.1126	benign	0.121	Stabilizing	0.864	D	0.549	neutral	N	0.487148322	None	None	N
K/R	0.0753	likely_benign	0.0703	benign	-0.001	Destabilizing	0.013	N	0.322	neutral	N	0.449110009	None	None	N
K/S	0.2519	likely_benign	0.29	benign	-0.145	Destabilizing	0.547	D	0.495	neutral	None	None	None	None	N
K/T	0.1196	likely_benign	0.1559	benign	0.003	Stabilizing	0.013	N	0.32	neutral	N	0.467349053	None	None	N
K/V	0.3334	likely_benign	0.3598	ambiguous	0.382	Stabilizing	0.809	D	0.561	neutral	None	None	None	None	N
K/W	0.774	likely_pathogenic	0.7339	pathogenic	-0.205	Destabilizing	0.995	D	0.673	neutral	None	None	None	None	N
K/Y	0.6326	likely_pathogenic	0.6209	pathogenic	0.146	Stabilizing	0.945	D	0.635	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.