TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9071	27436;27437;27438	chr2:178712814;178712813;178712812	chr2:179577541;179577540;179577539
N2AB	8754	26485;26486;26487	chr2:178712814;178712813;178712812	chr2:179577541;179577540;179577539
N2A	7827	23704;23705;23706	chr2:178712814;178712813;178712812	chr2:179577541;179577540;179577539
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: 53
• Structural Position: 131
• Q(SASA): 0.6979
• 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/N	None	None	0.002	N	0.123	0.146	0.134241683229	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85829E-06	0	0
D/V	rs886044486	0.227	0.117	N	0.34	0.189	0.36453787251	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.7E-05	None	0	0	None	0	None	0	0	0
D/V	rs886044486	0.227	0.117	N	0.34	0.189	0.36453787251	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
D/V	rs886044486	0.227	0.117	N	0.34	0.189	0.36453787251	gnomAD-4.0.0	5.12447E-06	None	None	None	None	N	None	0	6.78127E-05	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
D/A	0.1409	likely_benign	0.1445	benign	0.07	Stabilizing	0.027	N	0.295	neutral	N	0.45621232	None	None	N
D/C	0.5504	ambiguous	0.5716	pathogenic	-0.176	Destabilizing	0.935	D	0.325	neutral	None	None	None	None	N
D/E	0.1439	likely_benign	0.1244	benign	-0.438	Destabilizing	None	N	0.089	neutral	N	0.476949105	None	None	N
D/F	0.4343	ambiguous	0.4679	ambiguous	-0.086	Destabilizing	0.791	D	0.317	neutral	None	None	None	None	N
D/G	0.091	likely_benign	0.0907	benign	-0.012	Destabilizing	None	N	0.091	neutral	N	0.4357717	None	None	N
D/H	0.2163	likely_benign	0.232	benign	0.546	Stabilizing	0.484	N	0.313	neutral	N	0.505349215	None	None	N
D/I	0.3189	likely_benign	0.3375	benign	0.216	Stabilizing	0.38	N	0.353	neutral	None	None	None	None	N
D/K	0.2316	likely_benign	0.2463	benign	0.401	Stabilizing	0.081	N	0.302	neutral	None	None	None	None	N
D/L	0.3165	likely_benign	0.3302	benign	0.216	Stabilizing	0.149	N	0.34	neutral	None	None	None	None	N
D/M	0.4987	ambiguous	0.495	ambiguous	-0.003	Destabilizing	0.935	D	0.313	neutral	None	None	None	None	N
D/N	0.08	likely_benign	0.0787	benign	0.193	Stabilizing	0.002	N	0.123	neutral	N	0.447127631	None	None	N
D/P	0.5397	ambiguous	0.5407	ambiguous	0.185	Stabilizing	0.555	D	0.355	neutral	None	None	None	None	N
D/Q	0.2596	likely_benign	0.2559	benign	0.178	Stabilizing	0.235	N	0.277	neutral	None	None	None	None	N
D/R	0.2664	likely_benign	0.2964	benign	0.593	Stabilizing	0.235	N	0.337	neutral	None	None	None	None	N
D/S	0.1083	likely_benign	0.1083	benign	0.113	Stabilizing	0.035	N	0.221	neutral	None	None	None	None	N
D/T	0.2109	likely_benign	0.2115	benign	0.185	Stabilizing	0.002	N	0.167	neutral	None	None	None	None	N
D/V	0.1904	likely_benign	0.2031	benign	0.185	Stabilizing	0.117	N	0.34	neutral	N	0.469000657	None	None	N
D/W	0.7341	likely_pathogenic	0.7679	pathogenic	-0.082	Destabilizing	0.935	D	0.408	neutral	None	None	None	None	N
D/Y	0.1403	likely_benign	0.1637	benign	0.126	Stabilizing	0.741	D	0.317	neutral	N	0.485129902	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.