TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27193	81802;81803;81804	chr2:178564555;178564554;178564553	chr2:179429282;179429281;179429280
N2AB	25552	76879;76880;76881	chr2:178564555;178564554;178564553	chr2:179429282;179429281;179429280
N2A	24625	74098;74099;74100	chr2:178564555;178564554;178564553	chr2:179429282;179429281;179429280
N2B	18128	54607;54608;54609	chr2:178564555;178564554;178564553	chr2:179429282;179429281;179429280
Novex-1	18253	54982;54983;54984	chr2:178564555;178564554;178564553	chr2:179429282;179429281;179429280
Novex-2	18320	55183;55184;55185	chr2:178564555;178564554;178564553	chr2:179429282;179429281;179429280
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-86
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.422
• 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/N	rs565307960	-1.306	0.942	N	0.483	0.291	0.186928172975	gnomAD-2.1.1	5.26E-05	None	None	None	None	N	None	6.51E-05	0	None	0	0	None	0	None	3.73622E-04	3.58E-05	0
K/N	rs565307960	-1.306	0.942	N	0.483	0.291	0.186928172975	gnomAD-4.0.0	6.84501E-07	None	None	None	None	N	None	2.98936E-05	0	None	0	0	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
K/A	0.34	ambiguous	0.3288	benign	-0.191	Destabilizing	0.86	D	0.534	neutral	None	None	None	None	N
K/C	0.7343	likely_pathogenic	0.7353	pathogenic	-0.491	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
K/D	0.7642	likely_pathogenic	0.7348	pathogenic	-0.228	Destabilizing	0.956	D	0.633	neutral	None	None	None	None	N
K/E	0.2551	likely_benign	0.2176	benign	-0.158	Destabilizing	0.698	D	0.472	neutral	N	0.469340848	None	None	N
K/F	0.8415	likely_pathogenic	0.8146	pathogenic	-0.213	Destabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
K/G	0.6405	likely_pathogenic	0.6166	pathogenic	-0.442	Destabilizing	0.86	D	0.613	neutral	None	None	None	None	N
K/H	0.473	ambiguous	0.4517	ambiguous	-0.571	Destabilizing	0.994	D	0.679	prob.neutral	None	None	None	None	N
K/I	0.3631	ambiguous	0.3197	benign	0.419	Stabilizing	0.97	D	0.749	deleterious	N	0.499348088	None	None	N
K/L	0.3783	ambiguous	0.3533	ambiguous	0.419	Stabilizing	0.86	D	0.613	neutral	None	None	None	None	N
K/M	0.2482	likely_benign	0.2256	benign	-0.089	Destabilizing	0.994	D	0.671	neutral	None	None	None	None	N
K/N	0.61	likely_pathogenic	0.5694	pathogenic	-0.184	Destabilizing	0.942	D	0.483	neutral	N	0.475167446	None	None	N
K/P	0.378	ambiguous	0.3739	ambiguous	0.243	Stabilizing	0.978	D	0.674	neutral	None	None	None	None	N
K/Q	0.1556	likely_benign	0.1388	benign	-0.206	Destabilizing	0.125	N	0.323	neutral	N	0.501626624	None	None	N
K/R	0.103	likely_benign	0.1	benign	-0.178	Destabilizing	0.014	N	0.204	neutral	N	0.477133612	None	None	N
K/S	0.5566	ambiguous	0.53	ambiguous	-0.604	Destabilizing	0.86	D	0.473	neutral	None	None	None	None	N
K/T	0.2677	likely_benign	0.2464	benign	-0.362	Destabilizing	0.942	D	0.623	neutral	N	0.472596552	None	None	N
K/V	0.3341	likely_benign	0.3081	benign	0.243	Stabilizing	0.956	D	0.681	prob.neutral	None	None	None	None	N
K/W	0.875	likely_pathogenic	0.8584	pathogenic	-0.268	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.7007	likely_pathogenic	0.6801	pathogenic	0.064	Stabilizing	0.993	D	0.751	deleterious	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.