TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9282	28069;28070;28071	chr2:178711986;178711985;178711984	chr2:179576713;179576712;179576711
N2AB	8965	27118;27119;27120	chr2:178711986;178711985;178711984	chr2:179576713;179576712;179576711
N2A	8038	24337;24338;24339	chr2:178711986;178711985;178711984	chr2:179576713;179576712;179576711
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-78
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.7867
• 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/R	rs771474147	0.104	0.014	N	0.225	0.277	0.126345400529	gnomAD-2.1.1	1.62E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.58E-05	0
S/R	rs771474147	0.104	0.014	N	0.225	0.277	0.126345400529	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
S/R	rs771474147	0.104	0.014	N	0.225	0.277	0.126345400529	gnomAD-4.0.0	7.72758E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.44615E-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	0.0881	likely_benign	0.0873	benign	-0.163	Destabilizing	0.176	N	0.185	neutral	None	None	None	None	I
S/C	0.1981	likely_benign	0.2041	benign	-0.448	Destabilizing	0.013	N	0.234	neutral	N	0.51055235	None	None	I
S/D	0.2914	likely_benign	0.3155	benign	-0.001	Destabilizing	0.543	D	0.177	neutral	None	None	None	None	I
S/E	0.4356	ambiguous	0.4505	ambiguous	-0.108	Destabilizing	0.031	N	0.147	neutral	None	None	None	None	I
S/F	0.2781	likely_benign	0.256	benign	-0.881	Destabilizing	0.893	D	0.271	neutral	None	None	None	None	I
S/G	0.0916	likely_benign	0.1057	benign	-0.215	Destabilizing	0.425	N	0.175	neutral	N	0.477054333	None	None	I
S/H	0.2938	likely_benign	0.3265	benign	-0.556	Destabilizing	0.944	D	0.244	neutral	None	None	None	None	I
S/I	0.1294	likely_benign	0.1423	benign	-0.163	Destabilizing	0.473	N	0.289	neutral	D	0.538718867	None	None	I
S/K	0.4898	ambiguous	0.5246	ambiguous	-0.458	Destabilizing	0.031	N	0.139	neutral	None	None	None	None	I
S/L	0.1219	likely_benign	0.1088	benign	-0.163	Destabilizing	0.007	N	0.164	neutral	None	None	None	None	I
S/M	0.1929	likely_benign	0.1932	benign	-0.16	Destabilizing	0.893	D	0.239	neutral	None	None	None	None	I
S/N	0.0972	likely_benign	0.1125	benign	-0.26	Destabilizing	0.642	D	0.231	neutral	N	0.509916113	None	None	I
S/P	0.3499	ambiguous	0.2743	benign	-0.138	Destabilizing	0.828	D	0.256	neutral	None	None	None	None	I
S/Q	0.4219	ambiguous	0.4518	ambiguous	-0.48	Destabilizing	0.085	N	0.237	neutral	None	None	None	None	I
S/R	0.3744	ambiguous	0.4309	ambiguous	-0.202	Destabilizing	0.014	N	0.225	neutral	N	0.514783215	None	None	I
S/T	0.0846	likely_benign	0.0821	benign	-0.355	Destabilizing	0.023	N	0.16	neutral	D	0.530214027	None	None	I
S/V	0.1688	likely_benign	0.1731	benign	-0.138	Destabilizing	0.329	N	0.263	neutral	None	None	None	None	I
S/W	0.4479	ambiguous	0.4673	ambiguous	-0.965	Destabilizing	0.995	D	0.234	neutral	None	None	None	None	I
S/Y	0.2355	likely_benign	0.2344	benign	-0.652	Destabilizing	0.981	D	0.267	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.