TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27333	82222;82223;82224	chr2:178564135;178564134;178564133	chr2:179428862;179428861;179428860
N2AB	25692	77299;77300;77301	chr2:178564135;178564134;178564133	chr2:179428862;179428861;179428860
N2A	24765	74518;74519;74520	chr2:178564135;178564134;178564133	chr2:179428862;179428861;179428860
N2B	18268	55027;55028;55029	chr2:178564135;178564134;178564133	chr2:179428862;179428861;179428860
Novex-1	18393	55402;55403;55404	chr2:178564135;178564134;178564133	chr2:179428862;179428861;179428860
Novex-2	18460	55603;55604;55605	chr2:178564135;178564134;178564133	chr2:179428862;179428861;179428860
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: Ig-140
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.2042
• 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	rs1277663410	0.315	0.001	N	0.382	0.179	0.312001716656	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/I	rs1277663410	0.315	0.001	N	0.382	0.179	0.312001716656	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	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	0.0715	likely_benign	0.0721	benign	-1.17	Destabilizing	0.09	N	0.455	neutral	N	0.519594388	None	None	N
T/C	0.2441	likely_benign	0.2597	benign	-0.953	Destabilizing	0.944	D	0.655	neutral	None	None	None	None	N
T/D	0.3653	ambiguous	0.405	ambiguous	-1.679	Destabilizing	0.388	N	0.629	neutral	None	None	None	None	N
T/E	0.259	likely_benign	0.2869	benign	-1.462	Destabilizing	0.241	N	0.629	neutral	None	None	None	None	N
T/F	0.1576	likely_benign	0.179	benign	-0.725	Destabilizing	0.69	D	0.653	neutral	None	None	None	None	N
T/G	0.2078	likely_benign	0.2239	benign	-1.608	Destabilizing	0.241	N	0.639	neutral	None	None	None	None	N
T/H	0.1993	likely_benign	0.2112	benign	-1.719	Destabilizing	0.944	D	0.67	neutral	None	None	None	None	N
T/I	0.1003	likely_benign	0.1096	benign	-0.014	Destabilizing	0.001	N	0.382	neutral	N	0.486156605	None	None	N
T/K	0.2077	likely_benign	0.223	benign	-0.701	Destabilizing	0.241	N	0.63	neutral	None	None	None	None	N
T/L	0.0759	likely_benign	0.0816	benign	-0.014	Destabilizing	0.054	N	0.506	neutral	None	None	None	None	N
T/M	0.0763	likely_benign	0.0796	benign	-0.064	Destabilizing	0.69	D	0.659	neutral	None	None	None	None	N
T/N	0.1108	likely_benign	0.1134	benign	-1.469	Destabilizing	0.457	N	0.641	neutral	N	0.507454597	None	None	N
T/P	0.6433	likely_pathogenic	0.6926	pathogenic	-0.367	Destabilizing	0.627	D	0.657	neutral	N	0.514604501	None	None	N
T/Q	0.1976	likely_benign	0.2094	benign	-1.184	Destabilizing	0.69	D	0.653	neutral	None	None	None	None	N
T/R	0.1514	likely_benign	0.164	benign	-0.955	Destabilizing	0.69	D	0.654	neutral	None	None	None	None	N
T/S	0.0834	likely_benign	0.0861	benign	-1.663	Destabilizing	0.001	N	0.355	neutral	N	0.420987619	None	None	N
T/V	0.0892	likely_benign	0.0948	benign	-0.367	Destabilizing	0.004	N	0.297	neutral	None	None	None	None	N
T/W	0.4672	ambiguous	0.524	ambiguous	-0.924	Destabilizing	0.981	D	0.685	prob.neutral	None	None	None	None	N
T/Y	0.1957	likely_benign	0.2217	benign	-0.541	Destabilizing	0.818	D	0.652	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.