TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33417	100474;100475;100476	chr2:178536498;178536497;178536496	chr2:179401225;179401224;179401223
N2AB	31776	95551;95552;95553	chr2:178536498;178536497;178536496	chr2:179401225;179401224;179401223
N2A	30849	92770;92771;92772	chr2:178536498;178536497;178536496	chr2:179401225;179401224;179401223
N2B	24352	73279;73280;73281	chr2:178536498;178536497;178536496	chr2:179401225;179401224;179401223
Novex-1	24477	73654;73655;73656	chr2:178536498;178536497;178536496	chr2:179401225;179401224;179401223
Novex-2	24544	73855;73856;73857	chr2:178536498;178536497;178536496	chr2:179401225;179401224;179401223
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-131
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8424
• 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
A/S	None	None	None	N	0.087	0.03	0.136095386433	gnomAD-4.0.0	1.72826E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.686E-05	0
A/V	None	None	0.062	N	0.377	0.125	0.149567049428	gnomAD-4.0.0	7.07895E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.19065E-07	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
A/C	0.519	ambiguous	0.4519	ambiguous	-0.905	Destabilizing	0.824	D	0.321	neutral	None	None	None	None	I
A/D	0.1766	likely_benign	0.1835	benign	-0.432	Destabilizing	0.317	N	0.408	neutral	N	0.411314051	None	None	I
A/E	0.1508	likely_benign	0.1752	benign	-0.576	Destabilizing	0.081	N	0.383	neutral	None	None	None	None	I
A/F	0.2255	likely_benign	0.2223	benign	-0.926	Destabilizing	0.38	N	0.436	neutral	None	None	None	None	I
A/G	0.14	likely_benign	0.1226	benign	-0.264	Destabilizing	0.062	N	0.38	neutral	N	0.439463445	None	None	I
A/H	0.3875	ambiguous	0.3748	ambiguous	-0.251	Destabilizing	0.824	D	0.419	neutral	None	None	None	None	I
A/I	0.1127	likely_benign	0.1097	benign	-0.459	Destabilizing	0.081	N	0.38	neutral	None	None	None	None	I
A/K	0.2613	likely_benign	0.3266	benign	-0.509	Destabilizing	0.081	N	0.393	neutral	None	None	None	None	I
A/L	0.1046	likely_benign	0.0974	benign	-0.459	Destabilizing	0.001	N	0.215	neutral	None	None	None	None	I
A/M	0.1659	likely_benign	0.1459	benign	-0.608	Destabilizing	0.38	N	0.334	neutral	None	None	None	None	I
A/N	0.1627	likely_benign	0.1457	benign	-0.268	Destabilizing	0.235	N	0.415	neutral	None	None	None	None	I
A/P	0.1793	likely_benign	0.1659	benign	-0.372	Destabilizing	None	N	0.229	neutral	N	0.464204387	None	None	I
A/Q	0.2183	likely_benign	0.231	benign	-0.505	Destabilizing	0.38	N	0.352	neutral	None	None	None	None	I
A/R	0.2641	likely_benign	0.3324	benign	-0.122	Destabilizing	0.38	N	0.361	neutral	None	None	None	None	I
A/S	0.0864	likely_benign	0.0784	benign	-0.468	Destabilizing	None	N	0.087	neutral	N	0.423800559	None	None	I
A/T	0.0767	likely_benign	0.0708	benign	-0.538	Destabilizing	0.062	N	0.377	neutral	N	0.451371162	None	None	I
A/V	0.0696	likely_benign	0.0732	benign	-0.372	Destabilizing	0.062	N	0.377	neutral	N	0.456529053	None	None	I
A/W	0.6812	likely_pathogenic	0.6861	pathogenic	-1.013	Destabilizing	0.935	D	0.546	neutral	None	None	None	None	I
A/Y	0.4236	ambiguous	0.3997	ambiguous	-0.711	Destabilizing	0.555	D	0.429	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.