TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20185	60778;60779;60780	chr2:178591172;178591171;178591170	chr2:179455899;179455898;179455897
N2AB	18544	55855;55856;55857	chr2:178591172;178591171;178591170	chr2:179455899;179455898;179455897
N2A	17617	53074;53075;53076	chr2:178591172;178591171;178591170	chr2:179455899;179455898;179455897
N2B	11120	33583;33584;33585	chr2:178591172;178591171;178591170	chr2:179455899;179455898;179455897
Novex-1	11245	33958;33959;33960	chr2:178591172;178591171;178591170	chr2:179455899;179455898;179455897
Novex-2	11312	34159;34160;34161	chr2:178591172;178591171;178591170	chr2:179455899;179455898;179455897
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: Fn3-34
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.2205
• 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	None	None	0.991	N	0.462	0.424	0.427829143865	gnomAD-4.0.0	2.40067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62504E-06	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	0.2369	likely_benign	0.2717	benign	-0.628	Destabilizing	0.76	D	0.452	neutral	N	0.484338614	None	None	N
T/C	0.7158	likely_pathogenic	0.7341	pathogenic	-0.346	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	N
T/D	0.5702	likely_pathogenic	0.5863	pathogenic	-1.516	Destabilizing	0.986	D	0.434	neutral	None	None	None	None	N
T/E	0.64	likely_pathogenic	0.6691	pathogenic	-1.416	Destabilizing	0.953	D	0.431	neutral	None	None	None	None	N
T/F	0.5155	ambiguous	0.5325	ambiguous	-0.252	Destabilizing	0.993	D	0.543	neutral	None	None	None	None	N
T/G	0.3605	ambiguous	0.3638	ambiguous	-0.968	Destabilizing	0.91	D	0.465	neutral	None	None	None	None	N
T/H	0.4907	ambiguous	0.4866	ambiguous	-1.433	Destabilizing	0.252	N	0.387	neutral	None	None	None	None	N
T/I	0.6288	likely_pathogenic	0.6495	pathogenic	0.234	Stabilizing	0.991	D	0.462	neutral	N	0.500089465	None	None	N
T/K	0.4433	ambiguous	0.4388	ambiguous	-1.028	Destabilizing	0.986	D	0.429	neutral	None	None	None	None	N
T/L	0.2225	likely_benign	0.2294	benign	0.234	Stabilizing	0.953	D	0.435	neutral	None	None	None	None	N
T/M	0.1661	likely_benign	0.1837	benign	0.436	Stabilizing	0.999	D	0.448	neutral	None	None	None	None	N
T/N	0.2136	likely_benign	0.2228	benign	-1.335	Destabilizing	0.939	D	0.427	neutral	N	0.47192867	None	None	N
T/P	0.682	likely_pathogenic	0.7398	pathogenic	-0.022	Destabilizing	0.991	D	0.461	neutral	N	0.514079117	None	None	N
T/Q	0.4804	ambiguous	0.489	ambiguous	-1.192	Destabilizing	0.986	D	0.466	neutral	None	None	None	None	N
T/R	0.4552	ambiguous	0.4587	ambiguous	-1.124	Destabilizing	0.986	D	0.463	neutral	None	None	None	None	N
T/S	0.1415	likely_benign	0.1501	benign	-1.321	Destabilizing	0.17	N	0.309	neutral	N	0.506629799	None	None	N
T/V	0.5309	ambiguous	0.5416	ambiguous	-0.022	Destabilizing	0.953	D	0.439	neutral	None	None	None	None	N
T/W	0.8762	likely_pathogenic	0.8784	pathogenic	-0.555	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
T/Y	0.5869	likely_pathogenic	0.5858	pathogenic	-0.25	Destabilizing	0.986	D	0.538	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.