TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9080	27463;27464;27465	chr2:178712787;178712786;178712785	chr2:179577514;179577513;179577512
N2AB	8763	26512;26513;26514	chr2:178712787;178712786;178712785	chr2:179577514;179577513;179577512
N2A	7836	23731;23732;23733	chr2:178712787;178712786;178712785	chr2:179577514;179577513;179577512
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-76
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.601
• 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
D/E	rs1418163017	None	None	N	0.144	0.049	0.0716867268079	gnomAD-4.0.0	6.84218E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99467E-07	0	0
D/N	rs1405635875	-0.376	None	N	0.101	0.109	0.104622674875	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/N	rs1405635875	-0.376	None	N	0.101	0.109	0.104622674875	gnomAD-4.0.0	4.10535E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49738E-06	0	1.65667E-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
D/A	0.1109	likely_benign	0.1176	benign	-0.43	Destabilizing	0.012	N	0.241	neutral	N	0.468543053	None	None	N
D/C	0.4395	ambiguous	0.4479	ambiguous	0.173	Stabilizing	0.864	D	0.359	neutral	None	None	None	None	N
D/E	0.1238	likely_benign	0.1215	benign	-0.345	Destabilizing	None	N	0.144	neutral	N	0.4399323	None	None	N
D/F	0.4031	ambiguous	0.4383	ambiguous	-0.625	Destabilizing	0.001	N	0.19	neutral	None	None	None	None	N
D/G	0.1122	likely_benign	0.1193	benign	-0.621	Destabilizing	None	N	0.154	neutral	N	0.477181179	None	None	N
D/H	0.1443	likely_benign	0.1597	benign	-0.771	Destabilizing	0.344	N	0.333	neutral	N	0.50381042	None	None	N
D/I	0.3049	likely_benign	0.3421	ambiguous	0.027	Stabilizing	0.214	N	0.461	neutral	None	None	None	None	N
D/K	0.2014	likely_benign	0.2253	benign	0.221	Stabilizing	0.001	N	0.197	neutral	None	None	None	None	N
D/L	0.2491	likely_benign	0.2832	benign	0.027	Stabilizing	0.038	N	0.359	neutral	None	None	None	None	N
D/M	0.452	ambiguous	0.4722	ambiguous	0.45	Stabilizing	0.628	D	0.371	neutral	None	None	None	None	N
D/N	0.0751	likely_benign	0.0778	benign	0.034	Stabilizing	None	N	0.101	neutral	N	0.387788539	None	None	N
D/P	0.6538	likely_pathogenic	0.7005	pathogenic	-0.104	Destabilizing	0.136	N	0.403	neutral	None	None	None	None	N
D/Q	0.1909	likely_benign	0.1935	benign	0.042	Stabilizing	0.038	N	0.229	neutral	None	None	None	None	N
D/R	0.1918	likely_benign	0.2141	benign	0.183	Stabilizing	None	N	0.153	neutral	None	None	None	None	N
D/S	0.0869	likely_benign	0.0892	benign	-0.099	Destabilizing	0.003	N	0.167	neutral	None	None	None	None	N
D/T	0.1972	likely_benign	0.2122	benign	0.049	Stabilizing	0.031	N	0.268	neutral	None	None	None	None	N
D/V	0.1843	likely_benign	0.2118	benign	-0.104	Destabilizing	0.055	N	0.408	neutral	N	0.461113845	None	None	N
D/W	0.7206	likely_pathogenic	0.7505	pathogenic	-0.554	Destabilizing	0.676	D	0.36	neutral	None	None	None	None	N
D/Y	0.1413	likely_benign	0.1682	benign	-0.412	Destabilizing	0.002	N	0.178	neutral	N	0.466291632	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.