TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2945	9058;9059;9060	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473
N2AB	2945	9058;9059;9060	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473
N2A	2945	9058;9059;9060	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473
N2B	2899	8920;8921;8922	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473
Novex-1	2899	8920;8921;8922	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473
Novex-2	2899	8920;8921;8922	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473
Novex-3	2945	9058;9059;9060	chr2:178769748;178769747;178769746	chr2:179634475;179634474;179634473

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-19
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.4112
• 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	0.005	N	0.128	0.105	0.139678290688	gnomAD-4.0.0	3.18102E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.76393E-05	0	0	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	0.0658	likely_benign	0.0683	benign	-0.59	Destabilizing	0.005	N	0.128	neutral	N	0.409391829	None	None	N
T/C	0.3026	likely_benign	0.4044	ambiguous	-0.281	Destabilizing	0.676	D	0.207	neutral	None	None	None	None	N
T/D	0.32	likely_benign	0.3544	ambiguous	-0.082	Destabilizing	0.038	N	0.261	neutral	None	None	None	None	N
T/E	0.2521	likely_benign	0.2454	benign	-0.156	Destabilizing	0.016	N	0.271	neutral	None	None	None	None	N
T/F	0.2318	likely_benign	0.249	benign	-1.04	Destabilizing	0.356	N	0.252	neutral	None	None	None	None	N
T/G	0.171	likely_benign	0.2084	benign	-0.733	Destabilizing	0.016	N	0.247	neutral	None	None	None	None	N
T/H	0.2384	likely_benign	0.2592	benign	-1.098	Destabilizing	0.356	N	0.239	neutral	None	None	None	None	N
T/I	0.1374	likely_benign	0.1413	benign	-0.323	Destabilizing	0.055	N	0.285	neutral	N	0.462689649	None	None	N
T/K	0.1916	likely_benign	0.1816	benign	-0.467	Destabilizing	None	N	0.123	neutral	N	0.364723941	None	None	N
T/L	0.0833	likely_benign	0.0862	benign	-0.323	Destabilizing	0.031	N	0.259	neutral	None	None	None	None	N
T/M	0.0868	likely_benign	0.087	benign	0.098	Stabilizing	0.628	D	0.204	neutral	None	None	None	None	N
T/N	0.1118	likely_benign	0.1241	benign	-0.217	Destabilizing	0.016	N	0.155	neutral	None	None	None	None	N
T/P	0.098	likely_benign	0.1017	benign	-0.384	Destabilizing	0.055	N	0.31	neutral	N	0.37000517	None	None	N
T/Q	0.207	likely_benign	0.2011	benign	-0.54	Destabilizing	0.072	N	0.259	neutral	None	None	None	None	N
T/R	0.1594	likely_benign	0.1469	benign	-0.141	Destabilizing	None	N	0.125	neutral	N	0.407431069	None	None	N
T/S	0.0743	likely_benign	0.0925	benign	-0.458	Destabilizing	None	N	0.092	neutral	N	0.404216078	None	None	N
T/V	0.1164	likely_benign	0.1173	benign	-0.384	Destabilizing	0.072	N	0.145	neutral	None	None	None	None	N
T/W	0.5201	ambiguous	0.5863	pathogenic	-0.969	Destabilizing	0.864	D	0.248	neutral	None	None	None	None	N
T/Y	0.2607	likely_benign	0.3087	benign	-0.717	Destabilizing	0.356	N	0.255	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.