TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7376	22351;22352;22353	chr2:178722773;178722772;178722771	chr2:179587500;179587499;179587498
N2AB	7059	21400;21401;21402	chr2:178722773;178722772;178722771	chr2:179587500;179587499;179587498
N2A	6132	18619;18620;18621	chr2:178722773;178722772;178722771	chr2:179587500;179587499;179587498
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-58
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4745
• 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
N/S	rs765538868	-0.588	0.96	N	0.489	0.211	0.206339911435	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	1.78E-05	0
N/S	rs765538868	-0.588	0.96	N	0.489	0.211	0.206339911435	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs765538868	-0.588	0.96	N	0.489	0.211	0.206339911435	gnomAD-4.0.0	2.56393E-06	None	None	None	None	N	None	1.69182E-05	0	None	0	0	None	0	0	2.39451E-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
N/A	0.4809	ambiguous	0.6246	pathogenic	-0.831	Destabilizing	0.836	D	0.624	neutral	None	None	None	None	N
N/C	0.5657	likely_pathogenic	0.6475	pathogenic	0.036	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
N/D	0.2044	likely_benign	0.2739	benign	-0.188	Destabilizing	0.98	D	0.526	neutral	N	0.471797655	None	None	N
N/E	0.637	likely_pathogenic	0.7702	pathogenic	-0.092	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
N/F	0.8055	likely_pathogenic	0.8739	pathogenic	-0.689	Destabilizing	0.739	D	0.523	neutral	None	None	None	None	N
N/G	0.3418	ambiguous	0.4603	ambiguous	-1.161	Destabilizing	0.257	N	0.242	neutral	None	None	None	None	N
N/H	0.1637	likely_benign	0.2003	benign	-0.866	Destabilizing	1.0	D	0.587	neutral	D	0.53629185	None	None	N
N/I	0.6969	likely_pathogenic	0.8036	pathogenic	0.004	Stabilizing	0.997	D	0.721	prob.delet.	D	0.536465209	None	None	N
N/K	0.4967	ambiguous	0.6347	pathogenic	-0.058	Destabilizing	0.998	D	0.517	neutral	N	0.472605731	None	None	N
N/L	0.5343	ambiguous	0.6428	pathogenic	0.004	Stabilizing	0.986	D	0.666	neutral	None	None	None	None	N
N/M	0.6187	likely_pathogenic	0.7294	pathogenic	0.346	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
N/P	0.9266	likely_pathogenic	0.9622	pathogenic	-0.244	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
N/Q	0.4998	ambiguous	0.6067	pathogenic	-0.648	Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
N/R	0.4988	ambiguous	0.612	pathogenic	-0.113	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	N
N/S	0.1093	likely_benign	0.1479	benign	-0.747	Destabilizing	0.96	D	0.489	neutral	N	0.456078841	None	None	N
N/T	0.3092	likely_benign	0.4389	ambiguous	-0.448	Destabilizing	0.987	D	0.521	neutral	N	0.478937058	None	None	N
N/V	0.6848	likely_pathogenic	0.7947	pathogenic	-0.244	Destabilizing	0.977	D	0.685	prob.neutral	None	None	None	None	N
N/W	0.9133	likely_pathogenic	0.9468	pathogenic	-0.461	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/Y	0.3323	likely_benign	0.404	ambiguous	-0.233	Destabilizing	0.998	D	0.716	prob.delet.	N	0.515551219	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.