TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5764	17515;17516;17517	chr2:178731476;178731475;178731474	chr2:179596203;179596202;179596201
N2AB	5447	16564;16565;16566	chr2:178731476;178731475;178731474	chr2:179596203;179596202;179596201
N2A	4520	13783;13784;13785	chr2:178731476;178731475;178731474	chr2:179596203;179596202;179596201
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: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-41
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1827
• 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/Q	None	None	0.794	N	0.579	0.299	0.705127555899	gnomAD-4.0.0	1.59152E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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	0.3219	likely_benign	0.3067	benign	-2.465	Highly Destabilizing	0.129	N	0.475	neutral	None	None	None	None	N
L/C	0.4587	ambiguous	0.4225	ambiguous	-1.845	Destabilizing	0.983	D	0.549	neutral	None	None	None	None	N
L/D	0.7516	likely_pathogenic	0.7123	pathogenic	-2.709	Highly Destabilizing	0.716	D	0.619	neutral	None	None	None	None	N
L/E	0.313	likely_benign	0.2829	benign	-2.555	Highly Destabilizing	0.418	N	0.624	neutral	None	None	None	None	N
L/F	0.0961	likely_benign	0.0864	benign	-1.541	Destabilizing	0.005	N	0.343	neutral	None	None	None	None	N
L/G	0.5718	likely_pathogenic	0.5564	ambiguous	-2.945	Highly Destabilizing	0.002	N	0.481	neutral	None	None	None	None	N
L/H	0.1712	likely_benign	0.1638	benign	-2.316	Highly Destabilizing	0.983	D	0.623	neutral	None	None	None	None	N
L/I	0.1064	likely_benign	0.0988	benign	-1.112	Destabilizing	0.101	N	0.45	neutral	N	0.493150709	None	None	N
L/K	0.241	likely_benign	0.211	benign	-1.845	Destabilizing	0.418	N	0.558	neutral	None	None	None	None	N
L/M	0.0827	likely_benign	0.0827	benign	-1.07	Destabilizing	0.027	N	0.363	neutral	None	None	None	None	N
L/N	0.3754	ambiguous	0.3358	benign	-2.019	Highly Destabilizing	0.716	D	0.629	neutral	None	None	None	None	N
L/P	0.9794	likely_pathogenic	0.9761	pathogenic	-1.541	Destabilizing	0.794	D	0.623	neutral	N	0.469836804	None	None	N
L/Q	0.0936	likely_benign	0.0948	benign	-2.008	Highly Destabilizing	0.794	D	0.579	neutral	N	0.479933482	None	None	N
L/R	0.1874	likely_benign	0.1725	benign	-1.422	Destabilizing	0.794	D	0.576	neutral	N	0.485512661	None	None	N
L/S	0.2657	likely_benign	0.2444	benign	-2.697	Highly Destabilizing	0.027	N	0.507	neutral	None	None	None	None	N
L/T	0.2284	likely_benign	0.2087	benign	-2.412	Highly Destabilizing	0.264	N	0.509	neutral	None	None	None	None	N
L/V	0.1075	likely_benign	0.1073	benign	-1.541	Destabilizing	0.007	N	0.266	neutral	N	0.51173647	None	None	N
L/W	0.1517	likely_benign	0.1424	benign	-1.863	Destabilizing	0.005	N	0.49	neutral	None	None	None	None	N
L/Y	0.2338	likely_benign	0.2131	benign	-1.605	Destabilizing	0.557	D	0.563	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.