TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25986	78181;78182;78183	chr2:178568176;178568175;178568174	chr2:179432903;179432902;179432901
N2AB	24345	73258;73259;73260	chr2:178568176;178568175;178568174	chr2:179432903;179432902;179432901
N2A	23418	70477;70478;70479	chr2:178568176;178568175;178568174	chr2:179432903;179432902;179432901
N2B	16921	50986;50987;50988	chr2:178568176;178568175;178568174	chr2:179432903;179432902;179432901
Novex-1	17046	51361;51362;51363	chr2:178568176;178568175;178568174	chr2:179432903;179432902;179432901
Novex-2	17113	51562;51563;51564	chr2:178568176;178568175;178568174	chr2:179432903;179432902;179432901
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-76
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.1927
• 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
Y/H	rs1706668829	None	0.988	N	0.587	0.256	0.324986149311	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
Y/A	0.9555	likely_pathogenic	0.9583	pathogenic	-0.626	Destabilizing	0.835	D	0.461	neutral	None	None	None	None	N
Y/C	0.7634	likely_pathogenic	0.7647	pathogenic	0.074	Stabilizing	0.997	D	0.722	deleterious	N	0.461196886	None	None	N
Y/D	0.8342	likely_pathogenic	0.8572	pathogenic	0.869	Stabilizing	0.012	N	0.49	neutral	N	0.459217067	None	None	N
Y/E	0.9792	likely_pathogenic	0.981	pathogenic	0.851	Stabilizing	0.717	D	0.455	neutral	None	None	None	None	N
Y/F	0.2258	likely_benign	0.2179	benign	-0.303	Destabilizing	0.959	D	0.625	neutral	N	0.478540672	None	None	N
Y/G	0.9485	likely_pathogenic	0.9499	pathogenic	-0.807	Destabilizing	0.947	D	0.539	neutral	None	None	None	None	N
Y/H	0.5705	likely_pathogenic	0.5755	pathogenic	0.242	Stabilizing	0.988	D	0.587	neutral	N	0.480400416	None	None	N
Y/I	0.9199	likely_pathogenic	0.9334	pathogenic	-0.174	Destabilizing	0.973	D	0.595	neutral	None	None	None	None	N
Y/K	0.9716	likely_pathogenic	0.9749	pathogenic	0.164	Stabilizing	0.947	D	0.616	neutral	None	None	None	None	N
Y/L	0.7389	likely_pathogenic	0.7594	pathogenic	-0.174	Destabilizing	0.911	D	0.651	prob.neutral	None	None	None	None	N
Y/M	0.9161	likely_pathogenic	0.9231	pathogenic	-0.095	Destabilizing	0.998	D	0.612	neutral	None	None	None	None	N
Y/N	0.6169	likely_pathogenic	0.6624	pathogenic	-0.071	Destabilizing	0.87	D	0.639	neutral	N	0.493502999	None	None	N
Y/P	0.9612	likely_pathogenic	0.9631	pathogenic	-0.305	Destabilizing	0.973	D	0.686	prob.delet.	None	None	None	None	N
Y/Q	0.9672	likely_pathogenic	0.9698	pathogenic	-0.003	Destabilizing	0.973	D	0.575	neutral	None	None	None	None	N
Y/R	0.9575	likely_pathogenic	0.962	pathogenic	0.39	Stabilizing	0.973	D	0.613	neutral	None	None	None	None	N
Y/S	0.8161	likely_pathogenic	0.8329	pathogenic	-0.474	Destabilizing	0.931	D	0.451	neutral	N	0.496388589	None	None	N
Y/T	0.9554	likely_pathogenic	0.9624	pathogenic	-0.402	Destabilizing	0.947	D	0.574	neutral	None	None	None	None	N
Y/V	0.8998	likely_pathogenic	0.9124	pathogenic	-0.305	Destabilizing	0.973	D	0.598	neutral	None	None	None	None	N
Y/W	0.7537	likely_pathogenic	0.7503	pathogenic	-0.449	Destabilizing	0.998	D	0.578	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.