TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25944	78055;78056;78057	chr2:178568302;178568301;178568300	chr2:179433029;179433028;179433027
N2AB	24303	73132;73133;73134	chr2:178568302;178568301;178568300	chr2:179433029;179433028;179433027
N2A	23376	70351;70352;70353	chr2:178568302;178568301;178568300	chr2:179433029;179433028;179433027
N2B	16879	50860;50861;50862	chr2:178568302;178568301;178568300	chr2:179433029;179433028;179433027
Novex-1	17004	51235;51236;51237	chr2:178568302;178568301;178568300	chr2:179433029;179433028;179433027
Novex-2	17071	51436;51437;51438	chr2:178568302;178568301;178568300	chr2:179433029;179433028;179433027
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-76
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.6588
• Predicted PPI site: I

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	0.067	N	0.217	0.13	0.15556083564	gnomAD-4.0.0	1.59192E-06	None	None	None	None	I	None	0	2.28749E-05	None	0	0	None	0	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	0.1247	likely_benign	0.1143	benign	-0.297	Destabilizing	0.067	N	0.217	neutral	N	0.48719589	None	None	I
T/C	0.7424	likely_pathogenic	0.6942	pathogenic	-0.162	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
T/D	0.9205	likely_pathogenic	0.9066	pathogenic	0.072	Stabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	I
T/E	0.8937	likely_pathogenic	0.8861	pathogenic	-0.022	Destabilizing	0.991	D	0.671	neutral	None	None	None	None	I
T/F	0.751	likely_pathogenic	0.7153	pathogenic	-0.885	Destabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
T/G	0.5029	ambiguous	0.444	ambiguous	-0.391	Destabilizing	0.938	D	0.589	neutral	None	None	None	None	I
T/H	0.7327	likely_pathogenic	0.6925	pathogenic	-0.712	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
T/I	0.6875	likely_pathogenic	0.7103	pathogenic	-0.172	Destabilizing	0.988	D	0.687	prob.neutral	N	0.477902925	None	None	I
T/K	0.7879	likely_pathogenic	0.786	pathogenic	-0.257	Destabilizing	0.991	D	0.658	neutral	None	None	None	None	I
T/L	0.3025	likely_benign	0.308	benign	-0.172	Destabilizing	0.938	D	0.603	neutral	None	None	None	None	I
T/M	0.1698	likely_benign	0.1708	benign	0.083	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	I
T/N	0.4129	ambiguous	0.3525	ambiguous	-0.005	Destabilizing	0.994	D	0.67	neutral	N	0.486811887	None	None	I
T/P	0.6577	likely_pathogenic	0.6383	pathogenic	-0.187	Destabilizing	0.994	D	0.689	prob.neutral	N	0.461196886	None	None	I
T/Q	0.6689	likely_pathogenic	0.6395	pathogenic	-0.285	Destabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
T/R	0.7264	likely_pathogenic	0.7177	pathogenic	0.031	Stabilizing	0.995	D	0.672	neutral	None	None	None	None	I
T/S	0.2404	likely_benign	0.2036	benign	-0.196	Destabilizing	0.919	D	0.453	neutral	N	0.445789197	None	None	I
T/V	0.4325	ambiguous	0.4285	ambiguous	-0.187	Destabilizing	0.938	D	0.533	neutral	None	None	None	None	I
T/W	0.9479	likely_pathogenic	0.9397	pathogenic	-0.898	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
T/Y	0.8052	likely_pathogenic	0.7652	pathogenic	-0.602	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I

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.