TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25155	75688;75689;75690	chr2:178570669;178570668;178570667	chr2:179435396;179435395;179435394
N2AB	23514	70765;70766;70767	chr2:178570669;178570668;178570667	chr2:179435396;179435395;179435394
N2A	22587	67984;67985;67986	chr2:178570669;178570668;178570667	chr2:179435396;179435395;179435394
N2B	16090	48493;48494;48495	chr2:178570669;178570668;178570667	chr2:179435396;179435395;179435394
Novex-1	16215	48868;48869;48870	chr2:178570669;178570668;178570667	chr2:179435396;179435395;179435394
Novex-2	16282	49069;49070;49071	chr2:178570669;178570668;178570667	chr2:179435396;179435395;179435394
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-134
• Domain position: 45
• Structural Position: 73
• Q(SASA): 0.4608
• 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/I	None	None	0.998	N	0.456	0.401	0.437314048365	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1117	likely_benign	0.1192	benign	-0.23	Destabilizing	0.333	N	0.244	neutral	N	0.453341527	None	None	N
T/C	0.5027	ambiguous	0.5369	ambiguous	-0.208	Destabilizing	1.0	D	0.451	neutral	None	None	None	None	N
T/D	0.3525	ambiguous	0.3711	ambiguous	0.202	Stabilizing	0.999	D	0.451	neutral	None	None	None	None	N
T/E	0.4316	ambiguous	0.4719	ambiguous	0.114	Stabilizing	0.999	D	0.435	neutral	None	None	None	None	N
T/F	0.4304	ambiguous	0.4772	ambiguous	-0.812	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
T/G	0.2319	likely_benign	0.2332	benign	-0.327	Destabilizing	0.992	D	0.466	neutral	None	None	None	None	N
T/H	0.3332	likely_benign	0.3452	ambiguous	-0.602	Destabilizing	1.0	D	0.543	neutral	None	None	None	None	N
T/I	0.3932	ambiguous	0.4424	ambiguous	-0.1	Destabilizing	0.998	D	0.456	neutral	N	0.464099132	None	None	N
T/K	0.2942	likely_benign	0.3307	benign	-0.263	Destabilizing	0.998	D	0.436	neutral	N	0.457304552	None	None	N
T/L	0.1821	likely_benign	0.1975	benign	-0.1	Destabilizing	0.992	D	0.407	neutral	None	None	None	None	N
T/M	0.1383	likely_benign	0.1438	benign	0.012	Stabilizing	1.0	D	0.439	neutral	None	None	None	None	N
T/N	0.1216	likely_benign	0.1207	benign	-0.025	Destabilizing	1.0	D	0.427	neutral	None	None	None	None	N
T/P	0.3538	ambiguous	0.3788	ambiguous	-0.117	Destabilizing	0.998	D	0.445	neutral	N	0.50827209	None	None	N
T/Q	0.3487	ambiguous	0.3643	ambiguous	-0.249	Destabilizing	1.0	D	0.433	neutral	None	None	None	None	N
T/R	0.264	likely_benign	0.3026	benign	-0.006	Destabilizing	0.998	D	0.44	neutral	N	0.472543363	None	None	N
T/S	0.0992	likely_benign	0.0963	benign	-0.217	Destabilizing	0.978	D	0.379	neutral	N	0.393058285	None	None	N
T/V	0.2592	likely_benign	0.2981	benign	-0.117	Destabilizing	0.992	D	0.35	neutral	None	None	None	None	N
T/W	0.7791	likely_pathogenic	0.8119	pathogenic	-0.86	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
T/Y	0.4501	ambiguous	0.4977	ambiguous	-0.553	Destabilizing	1.0	D	0.55	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.