TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8978	27157;27158;27159	chr2:178713202;178713201;178713200	chr2:179577929;179577928;179577927
N2AB	8661	26206;26207;26208	chr2:178713202;178713201;178713200	chr2:179577929;179577928;179577927
N2A	7734	23425;23426;23427	chr2:178713202;178713201;178713200	chr2:179577929;179577928;179577927
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-75
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.9735
• 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/H	rs773744166	0.386	0.998	N	0.438	0.346	0.194818534648	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.16218E-04	None	0	0	None	0	None	0	0	0
D/H	rs773744166	0.386	0.998	N	0.438	0.346	0.194818534648	gnomAD-4.0.0	3.1832E-06	None	None	None	None	N	None	0	4.5754E-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	0.311	likely_benign	0.3343	benign	0.053	Stabilizing	0.925	D	0.471	neutral	N	0.471159284	None	None	N
D/C	0.8348	likely_pathogenic	0.844	pathogenic	0.087	Stabilizing	1.0	D	0.626	neutral	None	None	None	None	N
D/E	0.2345	likely_benign	0.2334	benign	-0.274	Destabilizing	0.961	D	0.401	neutral	N	0.470484493	None	None	N
D/F	0.8248	likely_pathogenic	0.8568	pathogenic	-0.153	Destabilizing	0.999	D	0.554	neutral	None	None	None	None	N
D/G	0.191	likely_benign	0.2146	benign	-0.041	Destabilizing	0.071	N	0.248	neutral	N	0.420418245	None	None	N
D/H	0.553	ambiguous	0.5639	ambiguous	0.33	Stabilizing	0.998	D	0.438	neutral	N	0.511005751	None	None	N
D/I	0.7273	likely_pathogenic	0.7746	pathogenic	0.23	Stabilizing	0.999	D	0.551	neutral	None	None	None	None	N
D/K	0.6444	likely_pathogenic	0.6525	pathogenic	0.524	Stabilizing	0.503	D	0.27	neutral	None	None	None	None	N
D/L	0.6945	likely_pathogenic	0.7238	pathogenic	0.23	Stabilizing	0.996	D	0.555	neutral	None	None	None	None	N
D/M	0.8353	likely_pathogenic	0.8605	pathogenic	0.158	Stabilizing	1.0	D	0.575	neutral	None	None	None	None	N
D/N	0.1422	likely_benign	0.1553	benign	0.407	Stabilizing	0.433	N	0.218	neutral	N	0.467060186	None	None	N
D/P	0.86	likely_pathogenic	0.8574	pathogenic	0.189	Stabilizing	0.999	D	0.428	neutral	None	None	None	None	N
D/Q	0.5569	ambiguous	0.5642	pathogenic	0.386	Stabilizing	0.991	D	0.408	neutral	None	None	None	None	N
D/R	0.6519	likely_pathogenic	0.6565	pathogenic	0.639	Stabilizing	0.983	D	0.485	neutral	None	None	None	None	N
D/S	0.1921	likely_benign	0.2172	benign	0.303	Stabilizing	0.97	D	0.417	neutral	None	None	None	None	N
D/T	0.4983	ambiguous	0.5318	ambiguous	0.377	Stabilizing	0.991	D	0.417	neutral	None	None	None	None	N
D/V	0.4915	ambiguous	0.5475	ambiguous	0.189	Stabilizing	0.994	D	0.555	neutral	N	0.469988162	None	None	N
D/W	0.9456	likely_pathogenic	0.9529	pathogenic	-0.152	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/Y	0.4456	ambiguous	0.4852	ambiguous	0.063	Stabilizing	0.998	D	0.554	neutral	N	0.474761102	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.