TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18537	55834;55835;55836	chr2:178601388;178601387;178601386	chr2:179466115;179466114;179466113
N2AB	16896	50911;50912;50913	chr2:178601388;178601387;178601386	chr2:179466115;179466114;179466113
N2A	15969	48130;48131;48132	chr2:178601388;178601387;178601386	chr2:179466115;179466114;179466113
N2B	9472	28639;28640;28641	chr2:178601388;178601387;178601386	chr2:179466115;179466114;179466113
Novex-1	9597	29014;29015;29016	chr2:178601388;178601387;178601386	chr2:179466115;179466114;179466113
Novex-2	9664	29215;29216;29217	chr2:178601388;178601387;178601386	chr2:179466115;179466114;179466113
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: Fn3-22
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.4129
• 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	None	None	None	N	0.139	0.162	0.0551355673512	gnomAD-4.0.0	1.5935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86166E-06	0	0
T/I	rs1027035888	-0.189	0.055	N	0.369	0.21	0.288727942641	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
T/I	rs1027035888	-0.189	0.055	N	0.369	0.21	0.288727942641	gnomAD-4.0.0	1.59355E-06	None	None	None	None	N	None	5.67022E-05	0	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	0.0732	likely_benign	0.0813	benign	-1.015	Destabilizing	None	N	0.139	neutral	N	0.443138468	None	None	N
T/C	0.3294	likely_benign	0.3673	ambiguous	-0.511	Destabilizing	0.356	N	0.477	neutral	None	None	None	None	N
T/D	0.551	ambiguous	0.5762	pathogenic	0.144	Stabilizing	0.016	N	0.355	neutral	None	None	None	None	N
T/E	0.5609	ambiguous	0.5719	pathogenic	0.196	Stabilizing	0.016	N	0.371	neutral	None	None	None	None	N
T/F	0.2821	likely_benign	0.3153	benign	-1.011	Destabilizing	0.356	N	0.585	neutral	None	None	None	None	N
T/G	0.1767	likely_benign	0.1925	benign	-1.311	Destabilizing	0.007	N	0.369	neutral	None	None	None	None	N
T/H	0.3123	likely_benign	0.3206	benign	-1.396	Destabilizing	0.356	N	0.495	neutral	None	None	None	None	N
T/I	0.2051	likely_benign	0.2388	benign	-0.3	Destabilizing	0.055	N	0.369	neutral	N	0.493740647	None	None	N
T/K	0.5526	ambiguous	0.5931	pathogenic	-0.472	Destabilizing	0.012	N	0.365	neutral	N	0.459203999	None	None	N
T/L	0.1274	likely_benign	0.1441	benign	-0.3	Destabilizing	0.016	N	0.376	neutral	None	None	None	None	N
T/M	0.1182	likely_benign	0.1298	benign	-0.151	Destabilizing	0.628	D	0.477	neutral	None	None	None	None	N
T/N	0.126	likely_benign	0.131	benign	-0.553	Destabilizing	0.016	N	0.277	neutral	None	None	None	None	N
T/P	0.6073	likely_pathogenic	0.7188	pathogenic	-0.506	Destabilizing	0.055	N	0.373	neutral	N	0.503264207	None	None	N
T/Q	0.3363	likely_benign	0.344	ambiguous	-0.59	Destabilizing	0.072	N	0.407	neutral	None	None	None	None	N
T/R	0.4921	ambiguous	0.5544	ambiguous	-0.346	Destabilizing	0.055	N	0.415	neutral	N	0.443618471	None	None	N
T/S	0.0699	likely_benign	0.0698	benign	-0.948	Destabilizing	None	N	0.136	neutral	N	0.37169687	None	None	N
T/V	0.1377	likely_benign	0.157	benign	-0.506	Destabilizing	0.016	N	0.307	neutral	None	None	None	None	N
T/W	0.6994	likely_pathogenic	0.7382	pathogenic	-0.935	Destabilizing	0.864	D	0.5	neutral	None	None	None	None	N
T/Y	0.3215	likely_benign	0.3442	ambiguous	-0.682	Destabilizing	0.356	N	0.575	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.