TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6065	18418;18419;18420	chr2:178730207;178730206;178730205	chr2:179594934;179594933;179594932
N2AB	5748	17467;17468;17469	chr2:178730207;178730206;178730205	chr2:179594934;179594933;179594932
N2A	4821	14686;14687;14688	chr2:178730207;178730206;178730205	chr2:179594934;179594933;179594932
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-44
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4671
• 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	0.76	N	0.531	0.089	0.231231049324	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/N	None	None	0.322	N	0.272	0.206	0.332646915603	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.0797	likely_benign	0.0785	benign	-0.396	Destabilizing	0.76	D	0.531	neutral	N	0.514142922	None	None	N
T/C	0.4462	ambiguous	0.4132	ambiguous	-0.192	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
T/D	0.3283	likely_benign	0.3374	benign	0.452	Stabilizing	0.91	D	0.608	neutral	None	None	None	None	N
T/E	0.3167	likely_benign	0.3298	benign	0.376	Stabilizing	0.953	D	0.605	neutral	None	None	None	None	N
T/F	0.1871	likely_benign	0.1982	benign	-0.902	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	N
T/G	0.2023	likely_benign	0.1969	benign	-0.52	Destabilizing	0.91	D	0.639	neutral	None	None	None	None	N
T/H	0.2162	likely_benign	0.2053	benign	-0.837	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
T/I	0.1733	likely_benign	0.1815	benign	-0.188	Destabilizing	0.991	D	0.688	prob.neutral	N	0.488681751	None	None	N
T/K	0.1831	likely_benign	0.1808	benign	-0.223	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	N
T/L	0.107	likely_benign	0.1057	benign	-0.188	Destabilizing	0.953	D	0.613	neutral	None	None	None	None	N
T/M	0.1027	likely_benign	0.1028	benign	0.043	Stabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
T/N	0.1045	likely_benign	0.1061	benign	-0.002	Destabilizing	0.322	N	0.272	neutral	N	0.453518538	None	None	N
T/P	0.3489	ambiguous	0.3536	ambiguous	-0.229	Destabilizing	0.991	D	0.687	prob.neutral	N	0.488681751	None	None	N
T/Q	0.2204	likely_benign	0.2126	benign	-0.229	Destabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	N
T/R	0.1606	likely_benign	0.1549	benign	-0.003	Destabilizing	0.986	D	0.687	prob.neutral	None	None	None	None	N
T/S	0.0874	likely_benign	0.0859	benign	-0.27	Destabilizing	0.17	N	0.309	neutral	N	0.452075743	None	None	N
T/V	0.1469	likely_benign	0.1523	benign	-0.229	Destabilizing	0.953	D	0.607	neutral	None	None	None	None	N
T/W	0.5752	likely_pathogenic	0.5594	ambiguous	-0.888	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
T/Y	0.2285	likely_benign	0.226	benign	-0.6	Destabilizing	0.998	D	0.755	deleterious	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.