TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19132	57619;57620;57621	chr2:178597688;178597687;178597686	chr2:179462415;179462414;179462413
N2AB	17491	52696;52697;52698	chr2:178597688;178597687;178597686	chr2:179462415;179462414;179462413
N2A	16564	49915;49916;49917	chr2:178597688;178597687;178597686	chr2:179462415;179462414;179462413
N2B	10067	30424;30425;30426	chr2:178597688;178597687;178597686	chr2:179462415;179462414;179462413
Novex-1	10192	30799;30800;30801	chr2:178597688;178597687;178597686	chr2:179462415;179462414;179462413
Novex-2	10259	31000;31001;31002	chr2:178597688;178597687;178597686	chr2:179462415;179462414;179462413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-117
• Domain position: 38
• Structural Position: 56
• Q(SASA): 0.4242
• 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
T/A	None	None	None	N	0.108	0.143	0.180583059064	gnomAD-4.0.0	1.59218E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
T/S	rs1245250461	None	0.001	N	0.233	0.108	0.214338557667	gnomAD-4.0.0	2.05312E-06	None	None	None	None	N	None	0	2.23804E-05	None	0	0	None	0	0	8.99625E-07	0	1.657E-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
T/A	0.0517	likely_benign	0.0529	benign	-0.298	Destabilizing	None	N	0.108	neutral	N	0.427814804	None	None	N
T/C	0.2271	likely_benign	0.2177	benign	-0.285	Destabilizing	0.245	N	0.299	neutral	None	None	None	None	N
T/D	0.1374	likely_benign	0.1487	benign	0.213	Stabilizing	0.004	N	0.324	neutral	None	None	None	None	N
T/E	0.1183	likely_benign	0.1175	benign	0.141	Stabilizing	None	N	0.169	neutral	None	None	None	None	N
T/F	0.1398	likely_benign	0.1456	benign	-0.796	Destabilizing	0.245	N	0.448	neutral	None	None	None	None	N
T/G	0.1204	likely_benign	0.1257	benign	-0.426	Destabilizing	None	N	0.173	neutral	None	None	None	None	N
T/H	0.1454	likely_benign	0.1493	benign	-0.664	Destabilizing	0.497	N	0.385	neutral	None	None	None	None	N
T/I	0.0764	likely_benign	0.0773	benign	-0.081	Destabilizing	0.033	N	0.359	neutral	N	0.441592178	None	None	N
T/K	0.113	likely_benign	0.1256	benign	-0.336	Destabilizing	0.008	N	0.334	neutral	None	None	None	None	N
T/L	0.0633	likely_benign	0.0651	benign	-0.081	Destabilizing	0.009	N	0.339	neutral	None	None	None	None	N
T/M	0.0723	likely_benign	0.075	benign	-0.036	Destabilizing	0.245	N	0.293	neutral	None	None	None	None	N
T/N	0.0734	likely_benign	0.0746	benign	-0.133	Destabilizing	0.014	N	0.204	neutral	N	0.439109233	None	None	N
T/P	0.0496	likely_benign	0.0462	benign	-0.124	Destabilizing	None	N	0.181	neutral	N	0.382234443	None	None	N
T/Q	0.1182	likely_benign	0.1179	benign	-0.329	Destabilizing	0.018	N	0.355	neutral	None	None	None	None	N
T/R	0.1144	likely_benign	0.1358	benign	-0.064	Destabilizing	0.018	N	0.347	neutral	None	None	None	None	N
T/S	0.073	likely_benign	0.0715	benign	-0.337	Destabilizing	0.001	N	0.233	neutral	N	0.446227206	None	None	N
T/V	0.0685	likely_benign	0.0678	benign	-0.124	Destabilizing	0.004	N	0.23	neutral	None	None	None	None	N
T/W	0.3921	ambiguous	0.4117	ambiguous	-0.831	Destabilizing	0.788	D	0.379	neutral	None	None	None	None	N
T/Y	0.1652	likely_benign	0.168	benign	-0.533	Destabilizing	0.245	N	0.451	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.