TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5926	18001;18002;18003	chr2:178730757;178730756;178730755	chr2:179595484;179595483;179595482
N2AB	5609	17050;17051;17052	chr2:178730757;178730756;178730755	chr2:179595484;179595483;179595482
N2A	4682	14269;14270;14271	chr2:178730757;178730756;178730755	chr2:179595484;179595483;179595482
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-43
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7111
• 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	rs755607488	0.365	0.83	N	0.638	0.347	0.322510055762	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	0	8.78E-05	None	0	0	None	0	None	0	0	0
K/N	rs755607488	0.365	0.83	N	0.638	0.347	0.322510055762	gnomAD-4.0.0	6.87216E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03096E-07	0	0
K/Q	None	None	0.83	N	0.631	0.298	0.30212335484	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	0.7615	likely_pathogenic	0.7548	pathogenic	0.081	Stabilizing	0.648	D	0.573	neutral	None	None	None	None	N
K/C	0.9046	likely_pathogenic	0.8924	pathogenic	-0.339	Destabilizing	0.993	D	0.682	prob.neutral	None	None	None	None	N
K/D	0.8887	likely_pathogenic	0.8938	pathogenic	-0.195	Destabilizing	0.866	D	0.675	neutral	None	None	None	None	N
K/E	0.4901	ambiguous	0.4865	ambiguous	-0.196	Destabilizing	0.41	N	0.541	neutral	D	0.522439906	None	None	N
K/F	0.9545	likely_pathogenic	0.9497	pathogenic	-0.183	Destabilizing	0.98	D	0.649	neutral	None	None	None	None	N
K/G	0.7461	likely_pathogenic	0.7415	pathogenic	-0.079	Destabilizing	0.866	D	0.507	neutral	None	None	None	None	N
K/H	0.5242	ambiguous	0.5099	ambiguous	-0.21	Destabilizing	0.98	D	0.669	neutral	None	None	None	None	N
K/I	0.7809	likely_pathogenic	0.7678	pathogenic	0.421	Stabilizing	0.929	D	0.674	neutral	None	None	None	None	N
K/L	0.7079	likely_pathogenic	0.6857	pathogenic	0.421	Stabilizing	0.866	D	0.507	neutral	None	None	None	None	N
K/M	0.6361	likely_pathogenic	0.611	pathogenic	0.014	Stabilizing	0.991	D	0.673	neutral	N	0.505361336	None	None	N
K/N	0.7956	likely_pathogenic	0.8001	pathogenic	0.096	Stabilizing	0.83	D	0.638	neutral	N	0.489192411	None	None	N
K/P	0.8689	likely_pathogenic	0.8581	pathogenic	0.333	Stabilizing	0.929	D	0.678	prob.neutral	None	None	None	None	N
K/Q	0.2191	likely_benign	0.216	benign	-0.039	Destabilizing	0.83	D	0.631	neutral	N	0.519746317	None	None	N
K/R	0.0873	likely_benign	0.0855	benign	-0.057	Destabilizing	0.01	N	0.28	neutral	N	0.476302184	None	None	N
K/S	0.7911	likely_pathogenic	0.7891	pathogenic	-0.276	Destabilizing	0.648	D	0.587	neutral	None	None	None	None	N
K/T	0.5634	ambiguous	0.5566	ambiguous	-0.149	Destabilizing	0.83	D	0.627	neutral	N	0.500411195	None	None	N
K/V	0.7433	likely_pathogenic	0.731	pathogenic	0.333	Stabilizing	0.866	D	0.607	neutral	None	None	None	None	N
K/W	0.8928	likely_pathogenic	0.8748	pathogenic	-0.277	Destabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	N
K/Y	0.8893	likely_pathogenic	0.8743	pathogenic	0.077	Stabilizing	0.929	D	0.631	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.