TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31840	95743;95744;95745	chr2:178545592;178545591;178545590	chr2:179410319;179410318;179410317
N2AB	30199	90820;90821;90822	chr2:178545592;178545591;178545590	chr2:179410319;179410318;179410317
N2A	29272	88039;88040;88041	chr2:178545592;178545591;178545590	chr2:179410319;179410318;179410317
N2B	22775	68548;68549;68550	chr2:178545592;178545591;178545590	chr2:179410319;179410318;179410317
Novex-1	22900	68923;68924;68925	chr2:178545592;178545591;178545590	chr2:179410319;179410318;179410317
Novex-2	22967	69124;69125;69126	chr2:178545592;178545591;178545590	chr2:179410319;179410318;179410317
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-120
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3195
• Predicted PPI site: I

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/N	rs1696700303	None	None	N	0.241	0.081	0.197625483188	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs1696700303	None	None	N	0.241	0.081	0.197625483188	gnomAD-4.0.0	6.57194E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46977E-05	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	0.0749	likely_benign	0.081	benign	-0.742	Destabilizing	0.035	N	0.397	neutral	None	None	None	None	I
S/C	0.0795	likely_benign	0.0744	benign	-0.444	Destabilizing	0.915	D	0.393	neutral	N	0.46869944	None	None	I
S/D	0.3038	likely_benign	0.2584	benign	0.109	Stabilizing	0.081	N	0.302	neutral	None	None	None	None	I
S/E	0.3318	likely_benign	0.287	benign	0.105	Stabilizing	0.081	N	0.318	neutral	None	None	None	None	I
S/F	0.1798	likely_benign	0.1913	benign	-0.897	Destabilizing	0.791	D	0.423	neutral	None	None	None	None	I
S/G	0.0934	likely_benign	0.0885	benign	-0.986	Destabilizing	0.027	N	0.324	neutral	D	0.523503406	None	None	I
S/H	0.214	likely_benign	0.1758	benign	-1.368	Destabilizing	0.555	D	0.374	neutral	None	None	None	None	I
S/I	0.1068	likely_benign	0.0992	benign	-0.199	Destabilizing	0.484	N	0.453	neutral	N	0.428803734	None	None	I
S/K	0.3042	likely_benign	0.2566	benign	-0.598	Destabilizing	None	N	0.14	neutral	None	None	None	None	I
S/L	0.0772	likely_benign	0.0809	benign	-0.199	Destabilizing	0.149	N	0.389	neutral	None	None	None	None	I
S/M	0.1299	likely_benign	0.1322	benign	-0.003	Destabilizing	0.935	D	0.367	neutral	None	None	None	None	I
S/N	0.0962	likely_benign	0.0829	benign	-0.511	Destabilizing	None	N	0.241	neutral	N	0.481059351	None	None	I
S/P	0.5035	ambiguous	0.6317	pathogenic	-0.346	Destabilizing	0.555	D	0.398	neutral	None	None	None	None	I
S/Q	0.2529	likely_benign	0.2164	benign	-0.636	Destabilizing	0.235	N	0.385	neutral	None	None	None	None	I
S/R	0.2875	likely_benign	0.246	benign	-0.502	Destabilizing	None	N	0.241	neutral	N	0.493007141	None	None	I
S/T	0.0598	likely_benign	0.0608	benign	-0.581	Destabilizing	0.117	N	0.353	neutral	N	0.388877122	None	None	I
S/V	0.1179	likely_benign	0.1181	benign	-0.346	Destabilizing	0.38	N	0.419	neutral	None	None	None	None	I
S/W	0.3111	likely_benign	0.3092	benign	-0.855	Destabilizing	0.935	D	0.631	neutral	None	None	None	None	I
S/Y	0.1591	likely_benign	0.1514	benign	-0.6	Destabilizing	0.555	D	0.419	neutral	None	None	None	None	I

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.