TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9350	28273;28274;28275	chr2:178711188;178711187;178711186	chr2:179575915;179575914;179575913
N2AB	9033	27322;27323;27324	chr2:178711188;178711187;178711186	chr2:179575915;179575914;179575913
N2A	8106	24541;24542;24543	chr2:178711188;178711187;178711186	chr2:179575915;179575914;179575913
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-79
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3943
• 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
S/P	rs949256276	-0.098	0.999	None	0.641	0.465	0.564872276104	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
S/P	rs949256276	-0.098	0.999	None	0.641	0.465	0.564872276104	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85819E-06	0	0
S/T	None	None	0.4	None	0.276	0.113	0.254244900254	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85819E-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
S/A	0.0957	likely_benign	0.1078	benign	-0.754	Destabilizing	0.953	D	0.407	neutral	None	None	None	None	N
S/C	0.2256	likely_benign	0.2321	benign	-0.393	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
S/D	0.5049	ambiguous	0.5822	pathogenic	0.064	Stabilizing	0.993	D	0.491	neutral	None	None	None	None	N
S/E	0.5751	likely_pathogenic	0.6571	pathogenic	0.038	Stabilizing	0.993	D	0.471	neutral	None	None	None	None	N
S/F	0.2043	likely_benign	0.248	benign	-1.089	Destabilizing	0.996	D	0.718	prob.delet.	None	None	None	None	N
S/G	0.1592	likely_benign	0.1828	benign	-0.969	Destabilizing	0.993	D	0.463	neutral	None	None	None	None	N
S/H	0.3521	ambiguous	0.4031	ambiguous	-1.462	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
S/I	0.2031	likely_benign	0.2438	benign	-0.296	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
S/K	0.6689	likely_pathogenic	0.7517	pathogenic	-0.588	Destabilizing	0.993	D	0.479	neutral	None	None	None	None	N
S/L	0.1252	likely_benign	0.1456	benign	-0.296	Destabilizing	0.135	N	0.36	neutral	None	None	None	None	N
S/M	0.2583	likely_benign	0.2741	benign	-0.002	Destabilizing	0.996	D	0.645	neutral	None	None	None	None	N
S/N	0.2145	likely_benign	0.2415	benign	-0.458	Destabilizing	0.993	D	0.507	neutral	None	None	None	None	N
S/P	0.933	likely_pathogenic	0.9515	pathogenic	-0.416	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
S/Q	0.5172	ambiguous	0.6013	pathogenic	-0.609	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
S/R	0.5271	ambiguous	0.6444	pathogenic	-0.487	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	N
S/T	0.091	likely_benign	0.1019	benign	-0.517	Destabilizing	0.4	N	0.276	neutral	None	None	None	None	N
S/V	0.1869	likely_benign	0.2202	benign	-0.416	Destabilizing	0.971	D	0.583	neutral	None	None	None	None	N
S/W	0.4257	ambiguous	0.5277	ambiguous	-1.053	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
S/Y	0.1882	likely_benign	0.2257	benign	-0.793	Destabilizing	0.999	D	0.722	prob.delet.	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.