TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15490	46693;46694;46695	chr2:178619849;178619848;178619847	chr2:179484576;179484575;179484574
N2AB	13849	41770;41771;41772	chr2:178619849;178619848;178619847	chr2:179484576;179484575;179484574
N2A	12922	38989;38990;38991	chr2:178619849;178619848;178619847	chr2:179484576;179484575;179484574
N2B	6425	19498;19499;19500	chr2:178619849;178619848;178619847	chr2:179484576;179484575;179484574
Novex-1	6550	19873;19874;19875	chr2:178619849;178619848;178619847	chr2:179484576;179484575;179484574
Novex-2	6617	20074;20075;20076	chr2:178619849;178619848;178619847	chr2:179484576;179484575;179484574
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-107
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.3814
• 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
L/I	None	None	0.669	N	0.336	0.158	0.366466682447	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
L/A	0.1911	likely_benign	0.2125	benign	-0.815	Destabilizing	0.842	D	0.298	neutral	None	None	None	None	N
L/C	0.3562	ambiguous	0.4259	ambiguous	-0.69	Destabilizing	0.998	D	0.431	neutral	None	None	None	None	N
L/D	0.5585	ambiguous	0.6357	pathogenic	-0.304	Destabilizing	0.991	D	0.473	neutral	None	None	None	None	N
L/E	0.2667	likely_benign	0.2958	benign	-0.376	Destabilizing	0.974	D	0.456	neutral	None	None	None	None	N
L/F	0.0816	likely_benign	0.1082	benign	-0.662	Destabilizing	0.005	N	0.093	neutral	N	0.34787272	None	None	N
L/G	0.4744	ambiguous	0.5399	ambiguous	-1.019	Destabilizing	0.974	D	0.421	neutral	None	None	None	None	N
L/H	0.1309	likely_benign	0.1762	benign	-0.244	Destabilizing	0.934	D	0.477	neutral	N	0.418439716	None	None	N
L/I	0.0926	likely_benign	0.0975	benign	-0.388	Destabilizing	0.669	D	0.336	neutral	N	0.364242044	None	None	N
L/K	0.1997	likely_benign	0.2297	benign	-0.525	Destabilizing	0.974	D	0.441	neutral	None	None	None	None	N
L/M	0.1095	likely_benign	0.1166	benign	-0.424	Destabilizing	0.974	D	0.409	neutral	None	None	None	None	N
L/N	0.2794	likely_benign	0.3444	ambiguous	-0.343	Destabilizing	0.974	D	0.477	neutral	None	None	None	None	N
L/P	0.5716	likely_pathogenic	0.5585	ambiguous	-0.497	Destabilizing	0.989	D	0.483	neutral	N	0.443044416	None	None	N
L/Q	0.1146	likely_benign	0.1287	benign	-0.559	Destabilizing	0.991	D	0.467	neutral	None	None	None	None	N
L/R	0.1386	likely_benign	0.1567	benign	0.057	Stabilizing	0.966	D	0.458	neutral	N	0.417879788	None	None	N
L/S	0.1861	likely_benign	0.2043	benign	-0.829	Destabilizing	0.974	D	0.393	neutral	None	None	None	None	N
L/T	0.1399	likely_benign	0.1466	benign	-0.79	Destabilizing	0.974	D	0.341	neutral	None	None	None	None	N
L/V	0.0847	likely_benign	0.0863	benign	-0.497	Destabilizing	0.801	D	0.349	neutral	N	0.401207479	None	None	N
L/W	0.1543	likely_benign	0.2012	benign	-0.68	Destabilizing	0.993	D	0.452	neutral	None	None	None	None	N
L/Y	0.1586	likely_benign	0.2395	benign	-0.444	Destabilizing	0.016	N	0.22	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.