TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14420	43483;43484;43485	chr2:178632748;178632747;178632746	chr2:179497475;179497474;179497473
N2AB	12779	38560;38561;38562	chr2:178632748;178632747;178632746	chr2:179497475;179497474;179497473
N2A	11852	35779;35780;35781	chr2:178632748;178632747;178632746	chr2:179497475;179497474;179497473
N2B	5355	16288;16289;16290	chr2:178632748;178632747;178632746	chr2:179497475;179497474;179497473
Novex-1	5480	16663;16664;16665	chr2:178632748;178632747;178632746	chr2:179497475;179497474;179497473
Novex-2	5547	16864;16865;16866	chr2:178632748;178632747;178632746	chr2:179497475;179497474;179497473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-95
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7717
• 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
F/L	None	None	0.003	N	0.238	0.339	0.12205267543	gnomAD-4.0.0	1.36896E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-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
F/A	0.7869	likely_pathogenic	0.8243	pathogenic	-0.846	Destabilizing	0.742	D	0.408	neutral	None	None	None	None	N
F/C	0.7592	likely_pathogenic	0.7365	pathogenic	-0.369	Destabilizing	0.994	D	0.457	neutral	N	0.484957192	None	None	N
F/D	0.9175	likely_pathogenic	0.9401	pathogenic	0.671	Stabilizing	0.984	D	0.453	neutral	None	None	None	None	N
F/E	0.9325	likely_pathogenic	0.9537	pathogenic	0.652	Stabilizing	0.953	D	0.439	neutral	None	None	None	None	N
F/G	0.9292	likely_pathogenic	0.9393	pathogenic	-1.023	Destabilizing	0.854	D	0.437	neutral	None	None	None	None	N
F/H	0.7772	likely_pathogenic	0.7806	pathogenic	0.316	Stabilizing	0.91	D	0.399	neutral	None	None	None	None	N
F/I	0.5996	likely_pathogenic	0.6389	pathogenic	-0.398	Destabilizing	0.521	D	0.338	neutral	N	0.43888275	None	None	N
F/K	0.9277	likely_pathogenic	0.9474	pathogenic	-0.124	Destabilizing	0.953	D	0.439	neutral	None	None	None	None	N
F/L	0.9213	likely_pathogenic	0.9346	pathogenic	-0.398	Destabilizing	0.003	N	0.238	neutral	N	0.400520908	None	None	N
F/M	0.7655	likely_pathogenic	0.7851	pathogenic	-0.442	Destabilizing	0.91	D	0.361	neutral	None	None	None	None	N
F/N	0.8015	likely_pathogenic	0.8288	pathogenic	-0.154	Destabilizing	0.984	D	0.451	neutral	None	None	None	None	N
F/P	0.971	likely_pathogenic	0.9776	pathogenic	-0.53	Destabilizing	0.984	D	0.446	neutral	None	None	None	None	N
F/Q	0.9063	likely_pathogenic	0.924	pathogenic	-0.171	Destabilizing	0.984	D	0.443	neutral	None	None	None	None	N
F/R	0.8482	likely_pathogenic	0.8762	pathogenic	0.271	Stabilizing	0.953	D	0.45	neutral	None	None	None	None	N
F/S	0.6555	likely_pathogenic	0.6931	pathogenic	-0.768	Destabilizing	0.815	D	0.437	neutral	N	0.454424959	None	None	N
F/T	0.7557	likely_pathogenic	0.7824	pathogenic	-0.697	Destabilizing	0.742	D	0.423	neutral	None	None	None	None	N
F/V	0.5828	likely_pathogenic	0.6122	pathogenic	-0.53	Destabilizing	0.521	D	0.376	neutral	N	0.41999239	None	None	N
F/W	0.6381	likely_pathogenic	0.6266	pathogenic	-0.227	Destabilizing	0.953	D	0.377	neutral	None	None	None	None	N
F/Y	0.255	likely_benign	0.2449	benign	-0.23	Destabilizing	0.001	N	0.235	neutral	N	0.366932183	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.