TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24145	72658;72659;72660	chr2:178573699;178573698;178573697	chr2:179438426;179438425;179438424
N2AB	22504	67735;67736;67737	chr2:178573699;178573698;178573697	chr2:179438426;179438425;179438424
N2A	21577	64954;64955;64956	chr2:178573699;178573698;178573697	chr2:179438426;179438425;179438424
N2B	15080	45463;45464;45465	chr2:178573699;178573698;178573697	chr2:179438426;179438425;179438424
Novex-1	15205	45838;45839;45840	chr2:178573699;178573698;178573697	chr2:179438426;179438425;179438424
Novex-2	15272	46039;46040;46041	chr2:178573699;178573698;178573697	chr2:179438426;179438425;179438424
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-63
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.5777
• 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
F/L	rs758746801	-0.909	None	N	0.095	0.076	0.187945064343	gnomAD-2.1.1	9.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.9E-05	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
F/A	0.0939	likely_benign	0.1074	benign	-1.43	Destabilizing	0.002	N	0.285	neutral	None	None	None	None	N
F/C	0.0944	likely_benign	0.0991	benign	-0.427	Destabilizing	0.427	N	0.498	neutral	N	0.415007717	None	None	N
F/D	0.1961	likely_benign	0.2319	benign	0.227	Stabilizing	0.018	N	0.421	neutral	None	None	None	None	N
F/E	0.1924	likely_benign	0.2255	benign	0.229	Stabilizing	0.018	N	0.305	neutral	None	None	None	None	N
F/G	0.1538	likely_benign	0.1814	benign	-1.679	Destabilizing	0.004	N	0.275	neutral	None	None	None	None	N
F/H	0.1072	likely_benign	0.1174	benign	-0.135	Destabilizing	0.497	N	0.471	neutral	None	None	None	None	N
F/I	0.071	likely_benign	0.0786	benign	-0.75	Destabilizing	None	N	0.087	neutral	N	0.402097135	None	None	N
F/K	0.1279	likely_benign	0.1596	benign	-0.415	Destabilizing	0.004	N	0.264	neutral	None	None	None	None	N
F/L	0.1318	likely_benign	0.1515	benign	-0.75	Destabilizing	None	N	0.095	neutral	N	0.343126189	None	None	N
F/M	0.0998	likely_benign	0.1145	benign	-0.519	Destabilizing	0.022	N	0.389	neutral	None	None	None	None	N
F/N	0.0944	likely_benign	0.1131	benign	-0.307	Destabilizing	0.018	N	0.419	neutral	None	None	None	None	N
F/P	0.5503	ambiguous	0.6614	pathogenic	-0.961	Destabilizing	0.085	N	0.529	neutral	None	None	None	None	N
F/Q	0.1107	likely_benign	0.1235	benign	-0.416	Destabilizing	0.044	N	0.504	neutral	None	None	None	None	N
F/R	0.1158	likely_benign	0.1407	benign	0.175	Stabilizing	None	N	0.359	neutral	None	None	None	None	N
F/S	0.0674	likely_benign	0.0807	benign	-1.031	Destabilizing	None	N	0.209	neutral	N	0.296889681	None	None	N
F/T	0.1064	likely_benign	0.1255	benign	-0.937	Destabilizing	0.004	N	0.248	neutral	None	None	None	None	N
F/V	0.0711	likely_benign	0.0795	benign	-0.961	Destabilizing	0.001	N	0.221	neutral	N	0.387551757	None	None	N
F/W	0.186	likely_benign	0.2093	benign	-0.355	Destabilizing	0.497	N	0.449	neutral	None	None	None	None	N
F/Y	0.0716	likely_benign	0.0754	benign	-0.417	Destabilizing	0.028	N	0.413	neutral	N	0.402443852	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.