TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14550	43873;43874;43875	chr2:178632246;178632245;178632244	chr2:179496973;179496972;179496971
N2AB	12909	38950;38951;38952	chr2:178632246;178632245;178632244	chr2:179496973;179496972;179496971
N2A	11982	36169;36170;36171	chr2:178632246;178632245;178632244	chr2:179496973;179496972;179496971
N2B	5485	16678;16679;16680	chr2:178632246;178632245;178632244	chr2:179496973;179496972;179496971
Novex-1	5610	17053;17054;17055	chr2:178632246;178632245;178632244	chr2:179496973;179496972;179496971
Novex-2	5677	17254;17255;17256	chr2:178632246;178632245;178632244	chr2:179496973;179496972;179496971
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-96
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.2513
• 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/P	rs2059896873	None	0.568	N	0.585	0.301	0.373537453441	gnomAD-4.0.0	6.86621E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01448E-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
T/A	0.108	likely_benign	0.0992	benign	-0.636	Destabilizing	0.037	N	0.299	neutral	N	0.495398812	None	None	N
T/C	0.4247	ambiguous	0.4159	ambiguous	-0.507	Destabilizing	0.859	D	0.519	neutral	None	None	None	None	N
T/D	0.4272	ambiguous	0.3886	ambiguous	-1.28	Destabilizing	0.364	N	0.519	neutral	None	None	None	None	N
T/E	0.2713	likely_benign	0.2335	benign	-1.254	Destabilizing	0.22	N	0.499	neutral	None	None	None	None	N
T/F	0.1332	likely_benign	0.1222	benign	-0.682	Destabilizing	None	N	0.258	neutral	None	None	None	None	N
T/G	0.3401	ambiguous	0.3031	benign	-0.918	Destabilizing	0.364	N	0.521	neutral	None	None	None	None	N
T/H	0.2113	likely_benign	0.1854	benign	-1.326	Destabilizing	0.859	D	0.578	neutral	None	None	None	None	N
T/I	0.0659	likely_benign	0.0648	benign	0.033	Stabilizing	None	N	0.177	neutral	N	0.447556671	None	None	N
T/K	0.1342	likely_benign	0.1116	benign	-0.862	Destabilizing	0.004	N	0.199	neutral	None	None	None	None	N
T/L	0.0751	likely_benign	0.0703	benign	0.033	Stabilizing	0.004	N	0.328	neutral	None	None	None	None	N
T/M	0.0767	likely_benign	0.0702	benign	0.407	Stabilizing	0.497	N	0.548	neutral	None	None	None	None	N
T/N	0.1195	likely_benign	0.1051	benign	-1.023	Destabilizing	0.301	N	0.446	neutral	N	0.500388029	None	None	N
T/P	0.4625	ambiguous	0.4354	ambiguous	-0.157	Destabilizing	0.568	D	0.585	neutral	N	0.515160847	None	None	N
T/Q	0.1978	likely_benign	0.1698	benign	-1.206	Destabilizing	0.497	N	0.577	neutral	None	None	None	None	N
T/R	0.1041	likely_benign	0.0885	benign	-0.631	Destabilizing	0.124	N	0.562	neutral	None	None	None	None	N
T/S	0.1416	likely_benign	0.1275	benign	-1.103	Destabilizing	0.081	N	0.371	neutral	N	0.484623344	None	None	N
T/V	0.0949	likely_benign	0.0895	benign	-0.157	Destabilizing	0.001	N	0.105	neutral	None	None	None	None	N
T/W	0.4443	ambiguous	0.3974	ambiguous	-0.734	Destabilizing	0.958	D	0.554	neutral	None	None	None	None	N
T/Y	0.1918	likely_benign	0.1765	benign	-0.439	Destabilizing	0.124	N	0.565	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.