TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6589	19990;19991;19992	chr2:178727813;178727812;178727811	chr2:179592540;179592539;179592538
N2AB	6272	19039;19040;19041	chr2:178727813;178727812;178727811	chr2:179592540;179592539;179592538
N2A	5345	16258;16259;16260	chr2:178727813;178727812;178727811	chr2:179592540;179592539;179592538
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-50
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2276
• 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
S/C	rs1206769574	-0.79	0.999	N	0.345	0.332	0.321108458156	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
S/C	rs1206769574	-0.79	0.999	N	0.345	0.332	0.321108458156	gnomAD-4.0.0	6.84978E-07	None	None	None	None	N	None	2.99365E-05	0	None	0	0	None	0	0	0	0	0
S/Y	None	None	0.996	N	0.428	0.386	0.504907739247	gnomAD-4.0.0	6.84978E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00182E-07	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
S/A	0.1	likely_benign	0.0929	benign	-0.721	Destabilizing	0.061	N	0.133	neutral	N	0.471794002	None	None	N
S/C	0.2076	likely_benign	0.1936	benign	-0.496	Destabilizing	0.999	D	0.345	neutral	N	0.479204873	None	None	N
S/D	0.5186	ambiguous	0.463	ambiguous	-0.201	Destabilizing	0.969	D	0.341	neutral	None	None	None	None	N
S/E	0.6323	likely_pathogenic	0.5894	pathogenic	-0.248	Destabilizing	0.969	D	0.35	neutral	None	None	None	None	N
S/F	0.3948	ambiguous	0.3188	benign	-1.113	Destabilizing	0.996	D	0.435	neutral	N	0.490725763	None	None	N
S/G	0.136	likely_benign	0.1213	benign	-0.906	Destabilizing	0.02	N	0.135	neutral	None	None	None	None	N
S/H	0.5393	ambiguous	0.4923	ambiguous	-1.441	Destabilizing	0.999	D	0.346	neutral	None	None	None	None	N
S/I	0.4052	ambiguous	0.3421	ambiguous	-0.345	Destabilizing	0.982	D	0.434	neutral	None	None	None	None	N
S/K	0.7956	likely_pathogenic	0.7437	pathogenic	-0.665	Destabilizing	0.939	D	0.342	neutral	None	None	None	None	N
S/L	0.1787	likely_benign	0.1456	benign	-0.345	Destabilizing	0.939	D	0.43	neutral	None	None	None	None	N
S/M	0.3068	likely_benign	0.2748	benign	0.043	Stabilizing	0.997	D	0.348	neutral	None	None	None	None	N
S/N	0.2618	likely_benign	0.2157	benign	-0.516	Destabilizing	0.969	D	0.379	neutral	None	None	None	None	N
S/P	0.9017	likely_pathogenic	0.8983	pathogenic	-0.439	Destabilizing	0.988	D	0.333	neutral	N	0.490218784	None	None	N
S/Q	0.6263	likely_pathogenic	0.6085	pathogenic	-0.781	Destabilizing	0.997	D	0.371	neutral	None	None	None	None	N
S/R	0.7315	likely_pathogenic	0.6656	pathogenic	-0.476	Destabilizing	0.991	D	0.347	neutral	None	None	None	None	N
S/T	0.1018	likely_benign	0.0883	benign	-0.599	Destabilizing	0.061	N	0.129	neutral	N	0.469465773	None	None	N
S/V	0.3285	likely_benign	0.2953	benign	-0.439	Destabilizing	0.939	D	0.426	neutral	None	None	None	None	N
S/W	0.5907	likely_pathogenic	0.5484	ambiguous	-1.044	Destabilizing	0.999	D	0.512	neutral	None	None	None	None	N
S/Y	0.338	likely_benign	0.2768	benign	-0.792	Destabilizing	0.996	D	0.428	neutral	N	0.478951384	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.