TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18033	54322;54323;54324	chr2:178605080;178605079;178605078	chr2:179469807;179469806;179469805
N2AB	16392	49399;49400;49401	chr2:178605080;178605079;178605078	chr2:179469807;179469806;179469805
N2A	15465	46618;46619;46620	chr2:178605080;178605079;178605078	chr2:179469807;179469806;179469805
N2B	8968	27127;27128;27129	chr2:178605080;178605079;178605078	chr2:179469807;179469806;179469805
Novex-1	9093	27502;27503;27504	chr2:178605080;178605079;178605078	chr2:179469807;179469806;179469805
Novex-2	9160	27703;27704;27705	chr2:178605080;178605079;178605078	chr2:179469807;179469806;179469805
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-114
• Domain position: 66
• Structural Position: 141
• Q(SASA): 0.2753
• 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
P/S	rs2054465796	None	0.709	N	0.713	0.196	0.368743488249	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
P/S	rs2054465796	None	0.709	N	0.713	0.196	0.368743488249	gnomAD-4.0.0	6.58172E-06	None	None	None	None	N	None	2.41464E-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
P/A	0.0986	likely_benign	0.095	benign	-1.365	Destabilizing	0.004	N	0.385	neutral	N	0.493287648	None	None	N
P/C	0.5205	ambiguous	0.5137	ambiguous	-0.714	Destabilizing	0.98	D	0.775	deleterious	None	None	None	None	N
P/D	0.4391	ambiguous	0.4146	ambiguous	-1.461	Destabilizing	0.866	D	0.804	deleterious	None	None	None	None	N
P/E	0.2804	likely_benign	0.2631	benign	-1.517	Destabilizing	0.866	D	0.789	deleterious	None	None	None	None	N
P/F	0.4659	ambiguous	0.4499	ambiguous	-1.208	Destabilizing	0.98	D	0.796	deleterious	None	None	None	None	N
P/G	0.2665	likely_benign	0.2485	benign	-1.627	Destabilizing	0.48	N	0.694	prob.neutral	None	None	None	None	N
P/H	0.2352	likely_benign	0.2251	benign	-1.242	Destabilizing	0.991	D	0.762	deleterious	N	0.507526381	None	None	N
P/I	0.2844	likely_benign	0.2819	benign	-0.758	Destabilizing	0.866	D	0.813	deleterious	None	None	None	None	N
P/K	0.237	likely_benign	0.2288	benign	-1.169	Destabilizing	0.866	D	0.801	deleterious	None	None	None	None	N
P/L	0.1276	likely_benign	0.1227	benign	-0.758	Destabilizing	0.709	D	0.765	deleterious	N	0.484110804	None	None	N
P/M	0.3082	likely_benign	0.2942	benign	-0.424	Destabilizing	0.98	D	0.763	deleterious	None	None	None	None	N
P/N	0.3067	likely_benign	0.2888	benign	-0.802	Destabilizing	0.929	D	0.807	deleterious	None	None	None	None	N
P/Q	0.1669	likely_benign	0.1556	benign	-1.067	Destabilizing	0.929	D	0.814	deleterious	None	None	None	None	N
P/R	0.1887	likely_benign	0.1808	benign	-0.566	Destabilizing	0.83	D	0.805	deleterious	N	0.473451093	None	None	N
P/S	0.1373	likely_benign	0.1241	benign	-1.202	Destabilizing	0.709	D	0.713	prob.delet.	N	0.471602867	None	None	N
P/T	0.1192	likely_benign	0.1099	benign	-1.169	Destabilizing	0.709	D	0.709	prob.delet.	N	0.476491398	None	None	N
P/V	0.2004	likely_benign	0.1973	benign	-0.927	Destabilizing	0.764	D	0.703	prob.neutral	None	None	None	None	N
P/W	0.6567	likely_pathogenic	0.6178	pathogenic	-1.361	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
P/Y	0.4675	ambiguous	0.4516	ambiguous	-1.113	Destabilizing	0.98	D	0.797	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.