TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18942	57049;57050;57051	chr2:178598886;178598885;178598884	chr2:179463613;179463612;179463611
N2AB	17301	52126;52127;52128	chr2:178598886;178598885;178598884	chr2:179463613;179463612;179463611
N2A	16374	49345;49346;49347	chr2:178598886;178598885;178598884	chr2:179463613;179463612;179463611
N2B	9877	29854;29855;29856	chr2:178598886;178598885;178598884	chr2:179463613;179463612;179463611
Novex-1	10002	30229;30230;30231	chr2:178598886;178598885;178598884	chr2:179463613;179463612;179463611
Novex-2	10069	30430;30431;30432	chr2:178598886;178598885;178598884	chr2:179463613;179463612;179463611
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-25
• Domain position: 59
• Structural Position: 85
• Q(SASA): 0.1139
• 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
M/T	None	None	0.811	N	0.525	0.316	0.687947222005	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
M/A	0.3716	ambiguous	0.2835	benign	-0.193	Destabilizing	0.737	D	0.427	neutral	None	None	None	None	N
M/C	0.7656	likely_pathogenic	0.7098	pathogenic	-0.45	Destabilizing	0.993	D	0.566	neutral	None	None	None	None	N
M/D	0.823	likely_pathogenic	0.7148	pathogenic	0.51	Stabilizing	0.98	D	0.608	neutral	None	None	None	None	N
M/E	0.5571	ambiguous	0.4448	ambiguous	0.457	Stabilizing	0.872	D	0.57	neutral	None	None	None	None	N
M/F	0.4287	ambiguous	0.3578	ambiguous	0.048	Stabilizing	0.872	D	0.485	neutral	None	None	None	None	N
M/G	0.5739	likely_pathogenic	0.4675	ambiguous	-0.342	Destabilizing	0.932	D	0.559	neutral	None	None	None	None	N
M/H	0.6151	likely_pathogenic	0.4784	ambiguous	0.383	Stabilizing	0.993	D	0.58	neutral	None	None	None	None	N
M/I	0.5485	ambiguous	0.4539	ambiguous	0.096	Stabilizing	0.514	D	0.365	neutral	N	0.498831461	None	None	N
M/K	0.2496	likely_benign	0.2022	benign	0.502	Stabilizing	0.514	D	0.476	neutral	N	0.455464686	None	None	N
M/L	0.1351	likely_benign	0.1312	benign	0.096	Stabilizing	0.002	N	0.189	neutral	N	0.42038932	None	None	N
M/N	0.5526	ambiguous	0.4174	ambiguous	0.58	Stabilizing	0.932	D	0.585	neutral	None	None	None	None	N
M/P	0.6789	likely_pathogenic	0.5414	ambiguous	0.027	Stabilizing	0.993	D	0.607	neutral	None	None	None	None	N
M/Q	0.2764	likely_benign	0.2035	benign	0.45	Stabilizing	0.872	D	0.481	neutral	None	None	None	None	N
M/R	0.2688	likely_benign	0.217	benign	0.924	Stabilizing	0.016	N	0.329	neutral	N	0.399534046	None	None	N
M/S	0.4497	ambiguous	0.3402	ambiguous	0.143	Stabilizing	0.932	D	0.541	neutral	None	None	None	None	N
M/T	0.2994	likely_benign	0.2244	benign	0.192	Stabilizing	0.811	D	0.525	neutral	N	0.389221052	None	None	N
M/V	0.1081	likely_benign	0.0954	benign	0.027	Stabilizing	0.316	N	0.32	neutral	N	0.479378909	None	None	N
M/W	0.7579	likely_pathogenic	0.6977	pathogenic	0.018	Stabilizing	0.998	D	0.573	neutral	None	None	None	None	N
M/Y	0.6908	likely_pathogenic	0.5765	pathogenic	0.212	Stabilizing	0.993	D	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.