TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20481	61666;61667;61668	chr2:178590284;178590283;178590282	chr2:179455011;179455010;179455009
N2AB	18840	56743;56744;56745	chr2:178590284;178590283;178590282	chr2:179455011;179455010;179455009
N2A	17913	53962;53963;53964	chr2:178590284;178590283;178590282	chr2:179455011;179455010;179455009
N2B	11416	34471;34472;34473	chr2:178590284;178590283;178590282	chr2:179455011;179455010;179455009
Novex-1	11541	34846;34847;34848	chr2:178590284;178590283;178590282	chr2:179455011;179455010;179455009
Novex-2	11608	35047;35048;35049	chr2:178590284;178590283;178590282	chr2:179455011;179455010;179455009
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-121
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.5151
• 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/S	None	None	0.885	N	0.508	0.066	0.208816687407	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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	0.1085	likely_benign	0.1258	benign	-0.258	Destabilizing	0.02	N	0.254	neutral	N	0.437929357	None	None	N
T/C	0.5371	ambiguous	0.5905	pathogenic	-0.246	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
T/D	0.6096	likely_pathogenic	0.6504	pathogenic	0.201	Stabilizing	0.993	D	0.712	prob.delet.	None	None	None	None	N
T/E	0.5549	ambiguous	0.6089	pathogenic	0.127	Stabilizing	0.986	D	0.687	prob.neutral	None	None	None	None	N
T/F	0.4612	ambiguous	0.5106	ambiguous	-0.761	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
T/G	0.27	likely_benign	0.3063	benign	-0.379	Destabilizing	0.91	D	0.592	neutral	None	None	None	None	N
T/H	0.4428	ambiguous	0.4757	ambiguous	-0.547	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
T/I	0.463	ambiguous	0.5113	ambiguous	-0.058	Destabilizing	0.982	D	0.717	prob.delet.	N	0.500055252	None	None	N
T/K	0.5319	ambiguous	0.554	ambiguous	-0.309	Destabilizing	0.986	D	0.689	prob.neutral	None	None	None	None	N
T/L	0.189	likely_benign	0.2191	benign	-0.058	Destabilizing	0.953	D	0.573	neutral	None	None	None	None	N
T/M	0.1561	likely_benign	0.1762	benign	-0.048	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
T/N	0.1718	likely_benign	0.2091	benign	-0.069	Destabilizing	0.991	D	0.644	neutral	N	0.425789566	None	None	N
T/P	0.3752	ambiguous	0.379	ambiguous	-0.096	Destabilizing	0.991	D	0.716	prob.delet.	N	0.500922043	None	None	N
T/Q	0.3856	ambiguous	0.4216	ambiguous	-0.267	Destabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	N
T/R	0.445	ambiguous	0.4573	ambiguous	-0.006	Destabilizing	0.993	D	0.712	prob.delet.	None	None	None	None	N
T/S	0.1198	likely_benign	0.1407	benign	-0.278	Destabilizing	0.885	D	0.508	neutral	N	0.437582641	None	None	N
T/V	0.3241	likely_benign	0.3702	ambiguous	-0.096	Destabilizing	0.91	D	0.509	neutral	None	None	None	None	N
T/W	0.7961	likely_pathogenic	0.8084	pathogenic	-0.811	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
T/Y	0.4978	ambiguous	0.5462	ambiguous	-0.512	Destabilizing	0.998	D	0.71	prob.delet.	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.