TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17305	52138;52139;52140	chr2:178609397;178609396;178609395	chr2:179474124;179474123;179474122
N2AB	15664	47215;47216;47217	chr2:178609397;178609396;178609395	chr2:179474124;179474123;179474122
N2A	14737	44434;44435;44436	chr2:178609397;178609396;178609395	chr2:179474124;179474123;179474122
N2B	8240	24943;24944;24945	chr2:178609397;178609396;178609395	chr2:179474124;179474123;179474122
Novex-1	8365	25318;25319;25320	chr2:178609397;178609396;178609395	chr2:179474124;179474123;179474122
Novex-2	8432	25519;25520;25521	chr2:178609397;178609396;178609395	chr2:179474124;179474123;179474122
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: Ig-112
• Domain position: 55
• Structural Position: 87
• Q(SASA): 0.2411
• 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/R	None	None	None	N	0.183	0.106	0.199424873507	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2532	likely_benign	0.2437	benign	-0.205	Destabilizing	0.127	N	0.545	neutral	None	None	None	None	N
K/C	0.6698	likely_pathogenic	0.6422	pathogenic	-0.745	Destabilizing	0.922	D	0.689	prob.neutral	None	None	None	None	N
K/D	0.4057	ambiguous	0.3976	ambiguous	-0.549	Destabilizing	0.068	N	0.521	neutral	None	None	None	None	N
K/E	0.1732	likely_benign	0.1634	benign	-0.578	Destabilizing	0.001	N	0.192	neutral	N	0.505718227	None	None	N
K/F	0.659	likely_pathogenic	0.6319	pathogenic	-0.627	Destabilizing	0.508	D	0.64	neutral	None	None	None	None	N
K/G	0.2929	likely_benign	0.2815	benign	-0.266	Destabilizing	0.127	N	0.517	neutral	None	None	None	None	N
K/H	0.296	likely_benign	0.287	benign	-0.293	Destabilizing	0.508	D	0.551	neutral	None	None	None	None	N
K/I	0.3055	likely_benign	0.2872	benign	-0.121	Destabilizing	0.508	D	0.633	neutral	None	None	None	None	N
K/L	0.3533	ambiguous	0.3363	benign	-0.121	Destabilizing	0.127	N	0.5	neutral	None	None	None	None	N
K/M	0.2813	likely_benign	0.2602	benign	-0.434	Destabilizing	0.9	D	0.553	neutral	N	0.507451811	None	None	N
K/N	0.3283	likely_benign	0.3069	benign	-0.321	Destabilizing	0.099	N	0.491	neutral	N	0.506585019	None	None	N
K/P	0.3079	likely_benign	0.3005	benign	-0.132	Destabilizing	0.508	D	0.531	neutral	None	None	None	None	N
K/Q	0.1448	likely_benign	0.1415	benign	-0.441	Destabilizing	0.052	N	0.523	neutral	N	0.506238302	None	None	N
K/R	0.0769	likely_benign	0.0758	benign	-0.397	Destabilizing	None	N	0.183	neutral	N	0.467487913	None	None	N
K/S	0.3205	likely_benign	0.3092	benign	-0.628	Destabilizing	0.127	N	0.487	neutral	None	None	None	None	N
K/T	0.1768	likely_benign	0.1708	benign	-0.575	Destabilizing	0.099	N	0.502	neutral	N	0.506585019	None	None	N
K/V	0.3103	likely_benign	0.2942	benign	-0.132	Destabilizing	0.338	N	0.515	neutral	None	None	None	None	N
K/W	0.6555	likely_pathogenic	0.6102	pathogenic	-0.753	Destabilizing	0.922	D	0.741	deleterious	None	None	None	None	N
K/Y	0.5398	ambiguous	0.5105	ambiguous	-0.445	Destabilizing	0.508	D	0.596	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.