TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26635	80128;80129;80130	chr2:178566229;178566228;178566227	chr2:179430956;179430955;179430954
N2AB	24994	75205;75206;75207	chr2:178566229;178566228;178566227	chr2:179430956;179430955;179430954
N2A	24067	72424;72425;72426	chr2:178566229;178566228;178566227	chr2:179430956;179430955;179430954
N2B	17570	52933;52934;52935	chr2:178566229;178566228;178566227	chr2:179430956;179430955;179430954
Novex-1	17695	53308;53309;53310	chr2:178566229;178566228;178566227	chr2:179430956;179430955;179430954
Novex-2	17762	53509;53510;53511	chr2:178566229;178566228;178566227	chr2:179430956;179430955;179430954
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-138
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.7754
• 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/G	rs1301645407	None	0.007	N	0.239	0.138	0.101711395817	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/G	rs1301645407	None	0.007	N	0.239	0.138	0.101711395817	gnomAD-4.0.0	2.56239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78668E-06	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	0.1291	likely_benign	0.1156	benign	0.091	Stabilizing	0.309	N	0.296	neutral	N	0.502692912	None	None	N
D/C	0.5098	ambiguous	0.4667	ambiguous	-0.098	Destabilizing	0.996	D	0.298	neutral	None	None	None	None	N
D/E	0.0848	likely_benign	0.0843	benign	-0.34	Destabilizing	0.003	N	0.166	neutral	N	0.410436112	None	None	N
D/F	0.6134	likely_pathogenic	0.5486	ambiguous	-0.09	Destabilizing	0.953	D	0.311	neutral	None	None	None	None	N
D/G	0.1123	likely_benign	0.1013	benign	0.003	Stabilizing	0.007	N	0.239	neutral	N	0.453378812	None	None	N
D/H	0.2335	likely_benign	0.2121	benign	0.527	Stabilizing	0.939	D	0.286	neutral	N	0.463467248	None	None	N
D/I	0.3399	likely_benign	0.3017	benign	0.251	Stabilizing	0.91	D	0.329	neutral	None	None	None	None	N
D/K	0.2347	likely_benign	0.2083	benign	0.431	Stabilizing	0.59	D	0.299	neutral	None	None	None	None	N
D/L	0.3383	likely_benign	0.3032	benign	0.251	Stabilizing	0.59	D	0.351	neutral	None	None	None	None	N
D/M	0.489	ambiguous	0.4575	ambiguous	0.046	Stabilizing	0.996	D	0.305	neutral	None	None	None	None	N
D/N	0.0909	likely_benign	0.0837	benign	0.296	Stabilizing	0.684	D	0.245	neutral	N	0.47494895	None	None	N
D/P	0.3492	ambiguous	0.3316	benign	0.216	Stabilizing	0.953	D	0.304	neutral	None	None	None	None	N
D/Q	0.209	likely_benign	0.1983	benign	0.273	Stabilizing	0.59	D	0.252	neutral	None	None	None	None	N
D/R	0.3007	likely_benign	0.2695	benign	0.626	Stabilizing	0.91	D	0.341	neutral	None	None	None	None	N
D/S	0.093	likely_benign	0.0865	benign	0.184	Stabilizing	0.101	N	0.229	neutral	None	None	None	None	N
D/T	0.1716	likely_benign	0.1565	benign	0.256	Stabilizing	0.009	N	0.252	neutral	None	None	None	None	N
D/V	0.2009	likely_benign	0.1758	benign	0.216	Stabilizing	0.521	D	0.356	neutral	N	0.470722177	None	None	N
D/W	0.8108	likely_pathogenic	0.7762	pathogenic	-0.09	Destabilizing	0.996	D	0.397	neutral	None	None	None	None	N
D/Y	0.2644	likely_benign	0.2265	benign	0.128	Stabilizing	0.979	D	0.308	neutral	N	0.466429763	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.