TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20214	60865;60866;60867	chr2:178591085;178591084;178591083	chr2:179455812;179455811;179455810
N2AB	18573	55942;55943;55944	chr2:178591085;178591084;178591083	chr2:179455812;179455811;179455810
N2A	17646	53161;53162;53163	chr2:178591085;178591084;178591083	chr2:179455812;179455811;179455810
N2B	11149	33670;33671;33672	chr2:178591085;178591084;178591083	chr2:179455812;179455811;179455810
Novex-1	11274	34045;34046;34047	chr2:178591085;178591084;178591083	chr2:179455812;179455811;179455810
Novex-2	11341	34246;34247;34248	chr2:178591085;178591084;178591083	chr2:179455812;179455811;179455810
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: Fn3-34
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.4379
• 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/K	None	None	0.379	N	0.395	0.246	0.243972157842	gnomAD-4.0.0	1.59223E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-05	0
T/S	rs1358705514	None	0.007	N	0.143	0.098	0.144782658237	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1358705514	None	0.007	N	0.143	0.098	0.144782658237	gnomAD-4.0.0	5.12719E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.57703E-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	0.0842	likely_benign	0.0828	benign	-0.769	Destabilizing	0.201	N	0.275	neutral	N	0.461068081	None	None	N
T/C	0.3361	likely_benign	0.3249	benign	-0.491	Destabilizing	0.992	D	0.463	neutral	None	None	None	None	N
T/D	0.4565	ambiguous	0.4656	ambiguous	-0.398	Destabilizing	0.617	D	0.38	neutral	None	None	None	None	N
T/E	0.3263	likely_benign	0.3383	benign	-0.387	Destabilizing	0.617	D	0.383	neutral	None	None	None	None	N
T/F	0.3067	likely_benign	0.3034	benign	-0.712	Destabilizing	0.92	D	0.565	neutral	None	None	None	None	N
T/G	0.2106	likely_benign	0.2138	benign	-1.046	Destabilizing	0.002	N	0.273	neutral	None	None	None	None	N
T/H	0.2681	likely_benign	0.2729	benign	-1.285	Destabilizing	0.977	D	0.553	neutral	None	None	None	None	N
T/I	0.1409	likely_benign	0.1366	benign	-0.116	Destabilizing	0.896	D	0.448	neutral	N	0.469111561	None	None	N
T/K	0.1393	likely_benign	0.1428	benign	-0.87	Destabilizing	0.379	N	0.395	neutral	N	0.454448753	None	None	N
T/L	0.092	likely_benign	0.0927	benign	-0.116	Destabilizing	0.617	D	0.397	neutral	None	None	None	None	N
T/M	0.0955	likely_benign	0.099	benign	0.124	Stabilizing	0.992	D	0.456	neutral	None	None	None	None	N
T/N	0.1442	likely_benign	0.1526	benign	-0.817	Destabilizing	0.447	N	0.374	neutral	None	None	None	None	N
T/P	0.1171	likely_benign	0.1208	benign	-0.301	Destabilizing	0.896	D	0.437	neutral	N	0.476826967	None	None	N
T/Q	0.2185	likely_benign	0.2251	benign	-0.953	Destabilizing	0.85	D	0.469	neutral	None	None	None	None	N
T/R	0.1271	likely_benign	0.138	benign	-0.614	Destabilizing	0.81	D	0.446	neutral	N	0.517596154	None	None	N
T/S	0.1114	likely_benign	0.1107	benign	-1.063	Destabilizing	0.007	N	0.143	neutral	N	0.416797229	None	None	N
T/V	0.1197	likely_benign	0.1129	benign	-0.301	Destabilizing	0.617	D	0.372	neutral	None	None	None	None	N
T/W	0.6567	likely_pathogenic	0.666	pathogenic	-0.674	Destabilizing	0.992	D	0.593	neutral	None	None	None	None	N
T/Y	0.3602	ambiguous	0.3596	ambiguous	-0.458	Destabilizing	0.972	D	0.563	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.