TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23202	69829;69830;69831	chr2:178576640;178576639;178576638	chr2:179441367;179441366;179441365
N2AB	21561	64906;64907;64908	chr2:178576640;178576639;178576638	chr2:179441367;179441366;179441365
N2A	20634	62125;62126;62127	chr2:178576640;178576639;178576638	chr2:179441367;179441366;179441365
N2B	14137	42634;42635;42636	chr2:178576640;178576639;178576638	chr2:179441367;179441366;179441365
Novex-1	14262	43009;43010;43011	chr2:178576640;178576639;178576638	chr2:179441367;179441366;179441365
Novex-2	14329	43210;43211;43212	chr2:178576640;178576639;178576638	chr2:179441367;179441366;179441365
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-56
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.5499
• 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	rs2046496039	None	0.001	N	0.127	0.082	0.130388298395	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs2046496039	None	0.001	N	0.127	0.082	0.130388298395	gnomAD-4.0.0	2.03007E-06	None	None	None	None	N	None	1.74709E-05	0	None	0	0	None	0	0	1.20499E-06	0	0
T/I	None	None	0.655	N	0.547	0.27	0.40528724903	gnomAD-4.0.0	1.59161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-05	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	0.0855	likely_benign	0.093	benign	-0.593	Destabilizing	0.001	N	0.127	neutral	N	0.505053719	None	None	N
T/C	0.4242	ambiguous	0.4426	ambiguous	-0.343	Destabilizing	0.951	D	0.481	neutral	None	None	None	None	N
T/D	0.5253	ambiguous	0.5347	ambiguous	0.187	Stabilizing	0.418	N	0.432	neutral	None	None	None	None	N
T/E	0.4412	ambiguous	0.4459	ambiguous	0.133	Stabilizing	0.129	N	0.419	neutral	None	None	None	None	N
T/F	0.2857	likely_benign	0.2738	benign	-0.922	Destabilizing	0.836	D	0.508	neutral	None	None	None	None	N
T/G	0.2042	likely_benign	0.1991	benign	-0.768	Destabilizing	0.129	N	0.395	neutral	None	None	None	None	N
T/H	0.2908	likely_benign	0.2898	benign	-1.022	Destabilizing	0.836	D	0.509	neutral	None	None	None	None	N
T/I	0.1882	likely_benign	0.2079	benign	-0.239	Destabilizing	0.655	D	0.547	neutral	N	0.484654555	None	None	N
T/K	0.2784	likely_benign	0.274	benign	-0.489	Destabilizing	0.213	N	0.443	neutral	N	0.478963195	None	None	N
T/L	0.105	likely_benign	0.1051	benign	-0.239	Destabilizing	0.264	N	0.441	neutral	None	None	None	None	N
T/M	0.0935	likely_benign	0.0972	benign	-0.006	Destabilizing	0.94	D	0.501	neutral	None	None	None	None	N
T/N	0.1292	likely_benign	0.1357	benign	-0.265	Destabilizing	0.264	N	0.314	neutral	None	None	None	None	N
T/P	0.1035	likely_benign	0.1013	benign	-0.327	Destabilizing	0.001	N	0.213	neutral	N	0.469055061	None	None	N
T/Q	0.25	likely_benign	0.25	benign	-0.493	Destabilizing	0.027	N	0.242	neutral	None	None	None	None	N
T/R	0.2535	likely_benign	0.2589	benign	-0.202	Destabilizing	0.351	N	0.504	neutral	N	0.515942716	None	None	N
T/S	0.0998	likely_benign	0.1003	benign	-0.548	Destabilizing	0.003	N	0.131	neutral	N	0.447389495	None	None	N
T/V	0.1403	likely_benign	0.1492	benign	-0.327	Destabilizing	0.264	N	0.322	neutral	None	None	None	None	N
T/W	0.5973	likely_pathogenic	0.5974	pathogenic	-0.862	Destabilizing	0.983	D	0.523	neutral	None	None	None	None	N
T/Y	0.3256	likely_benign	0.3291	benign	-0.614	Destabilizing	0.94	D	0.509	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.