TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7464	22615;22616;22617	chr2:178722397;178722396;178722395	chr2:179587124;179587123;179587122
N2AB	7147	21664;21665;21666	chr2:178722397;178722396;178722395	chr2:179587124;179587123;179587122
N2A	6220	18883;18884;18885	chr2:178722397;178722396;178722395	chr2:179587124;179587123;179587122
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-59
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.3935
• 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/D	rs879082137	None	0.805	N	0.437	0.161	0.233785782151	gnomAD-4.0.0	1.36869E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-05	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	0.4709	ambiguous	0.3374	benign	-0.623	Destabilizing	0.64	D	0.469	neutral	None	None	None	None	N
N/C	0.5719	likely_pathogenic	0.4333	ambiguous	0.231	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
N/D	0.2652	likely_benign	0.1984	benign	-0.408	Destabilizing	0.805	D	0.437	neutral	N	0.473413808	None	None	N
N/E	0.5998	likely_pathogenic	0.4691	ambiguous	-0.328	Destabilizing	0.329	N	0.255	neutral	None	None	None	None	N
N/F	0.5947	likely_pathogenic	0.4812	ambiguous	-0.38	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
N/G	0.4811	ambiguous	0.3988	ambiguous	-0.959	Destabilizing	0.95	D	0.413	neutral	None	None	None	None	N
N/H	0.1605	likely_benign	0.1233	benign	-0.88	Destabilizing	0.999	D	0.455	neutral	N	0.498021464	None	None	N
N/I	0.3235	likely_benign	0.2337	benign	0.224	Stabilizing	0.996	D	0.624	neutral	N	0.486124083	None	None	N
N/K	0.4078	ambiguous	0.2888	benign	-0.363	Destabilizing	0.99	D	0.399	neutral	N	0.435124778	None	None	N
N/L	0.3767	ambiguous	0.2988	benign	0.224	Stabilizing	0.994	D	0.563	neutral	None	None	None	None	N
N/M	0.4342	ambiguous	0.3539	ambiguous	0.627	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	N
N/P	0.8588	likely_pathogenic	0.7822	pathogenic	-0.027	Destabilizing	0.987	D	0.561	neutral	None	None	None	None	N
N/Q	0.4643	ambiguous	0.3595	ambiguous	-0.758	Destabilizing	0.994	D	0.437	neutral	None	None	None	None	N
N/R	0.4596	ambiguous	0.3357	benign	-0.493	Destabilizing	0.998	D	0.435	neutral	None	None	None	None	N
N/S	0.1928	likely_benign	0.1558	benign	-0.773	Destabilizing	0.101	N	0.143	neutral	N	0.490767417	None	None	N
N/T	0.2535	likely_benign	0.1833	benign	-0.514	Destabilizing	0.865	D	0.401	neutral	N	0.521186325	None	None	N
N/V	0.3877	ambiguous	0.2815	benign	-0.027	Destabilizing	0.938	D	0.583	neutral	None	None	None	None	N
N/W	0.8436	likely_pathogenic	0.7558	pathogenic	-0.242	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
N/Y	0.1711	likely_benign	0.132	benign	-0.036	Destabilizing	1.0	D	0.59	neutral	N	0.484731732	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.