TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15702	47329;47330;47331	chr2:178618354;178618353;178618352	chr2:179483081;179483080;179483079
N2AB	14061	42406;42407;42408	chr2:178618354;178618353;178618352	chr2:179483081;179483080;179483079
N2A	13134	39625;39626;39627	chr2:178618354;178618353;178618352	chr2:179483081;179483080;179483079
N2B	6637	20134;20135;20136	chr2:178618354;178618353;178618352	chr2:179483081;179483080;179483079
Novex-1	6762	20509;20510;20511	chr2:178618354;178618353;178618352	chr2:179483081;179483080;179483079
Novex-2	6829	20710;20711;20712	chr2:178618354;178618353;178618352	chr2:179483081;179483080;179483079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-1
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8921
• 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
K/M	None	None	1.0	N	0.659	0.541	0.376393476264	gnomAD-4.0.0	3.42319E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49948E-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
K/A	0.8714	likely_pathogenic	0.8045	pathogenic	-0.029	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
K/C	0.9707	likely_pathogenic	0.9397	pathogenic	-0.509	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/D	0.9165	likely_pathogenic	0.8423	pathogenic	-0.288	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
K/E	0.728	likely_pathogenic	0.6185	pathogenic	-0.31	Destabilizing	0.999	D	0.627	neutral	N	0.474528896	None	None	N
K/F	0.9848	likely_pathogenic	0.9733	pathogenic	-0.407	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
K/G	0.8302	likely_pathogenic	0.7096	pathogenic	-0.133	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/H	0.7539	likely_pathogenic	0.6567	pathogenic	-0.219	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/I	0.9099	likely_pathogenic	0.8821	pathogenic	0.161	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/L	0.8579	likely_pathogenic	0.8019	pathogenic	0.161	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/M	0.7739	likely_pathogenic	0.7149	pathogenic	-0.139	Destabilizing	1.0	D	0.659	neutral	N	0.472777114	None	None	N
K/N	0.8418	likely_pathogenic	0.7523	pathogenic	-0.044	Destabilizing	1.0	D	0.655	neutral	N	0.476941725	None	None	N
K/P	0.9009	likely_pathogenic	0.8347	pathogenic	0.119	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/Q	0.439	ambiguous	0.364	ambiguous	-0.19	Destabilizing	1.0	D	0.643	neutral	N	0.472239319	None	None	N
K/R	0.1575	likely_benign	0.1344	benign	-0.159	Destabilizing	0.999	D	0.574	neutral	N	0.476369479	None	None	N
K/S	0.881	likely_pathogenic	0.805	pathogenic	-0.411	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
K/T	0.7212	likely_pathogenic	0.6362	pathogenic	-0.325	Destabilizing	1.0	D	0.624	neutral	N	0.476773185	None	None	N
K/V	0.8737	likely_pathogenic	0.8323	pathogenic	0.119	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/W	0.9752	likely_pathogenic	0.9564	pathogenic	-0.509	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/Y	0.95	likely_pathogenic	0.921	pathogenic	-0.161	Destabilizing	1.0	D	0.693	prob.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.