TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9225	27898;27899;27900	chr2:178712157;178712156;178712155	chr2:179576884;179576883;179576882
N2AB	8908	26947;26948;26949	chr2:178712157;178712156;178712155	chr2:179576884;179576883;179576882
N2A	7981	24166;24167;24168	chr2:178712157;178712156;178712155	chr2:179576884;179576883;179576882
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-78
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4101
• 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
Q/P	None	None	0.917	N	0.515	0.429	0.506128173473	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8583E-06	0	0
Q/R	rs2076750199	None	0.006	N	0.189	0.16	0.183819452728	gnomAD-4.0.0	4.77371E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57491E-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
Q/A	0.3419	ambiguous	0.3971	ambiguous	-0.677	Destabilizing	0.495	N	0.432	neutral	None	None	None	None	I
Q/C	0.7037	likely_pathogenic	0.8086	pathogenic	-0.05	Destabilizing	0.995	D	0.528	neutral	None	None	None	None	I
Q/D	0.5473	ambiguous	0.649	pathogenic	-0.7	Destabilizing	0.329	N	0.359	neutral	None	None	None	None	I
Q/E	0.0949	likely_benign	0.1158	benign	-0.59	Destabilizing	0.01	N	0.185	neutral	N	0.442936185	None	None	I
Q/F	0.7142	likely_pathogenic	0.7703	pathogenic	-0.29	Destabilizing	0.893	D	0.531	neutral	None	None	None	None	I
Q/G	0.4808	ambiguous	0.5722	pathogenic	-1.054	Destabilizing	0.828	D	0.524	neutral	None	None	None	None	I
Q/H	0.2457	likely_benign	0.3083	benign	-0.903	Destabilizing	0.975	D	0.449	neutral	N	0.481169286	None	None	I
Q/I	0.3803	ambiguous	0.453	ambiguous	0.295	Stabilizing	0.543	D	0.547	neutral	None	None	None	None	I
Q/K	0.1322	likely_benign	0.164	benign	-0.439	Destabilizing	0.01	N	0.199	neutral	N	0.449632871	None	None	I
Q/L	0.1694	likely_benign	0.2375	benign	0.295	Stabilizing	0.002	N	0.373	neutral	N	0.515031144	None	None	I
Q/M	0.4488	ambiguous	0.5108	ambiguous	0.712	Stabilizing	0.893	D	0.447	neutral	None	None	None	None	I
Q/N	0.4169	ambiguous	0.476	ambiguous	-0.987	Destabilizing	0.828	D	0.344	neutral	None	None	None	None	I
Q/P	0.6797	likely_pathogenic	0.7764	pathogenic	0.003	Stabilizing	0.917	D	0.515	neutral	N	0.51089476	None	None	I
Q/R	0.1374	likely_benign	0.186	benign	-0.402	Destabilizing	0.006	N	0.189	neutral	N	0.486497748	None	None	I
Q/S	0.3259	likely_benign	0.338	benign	-1.08	Destabilizing	0.495	N	0.367	neutral	None	None	None	None	I
Q/T	0.2243	likely_benign	0.2525	benign	-0.772	Destabilizing	0.828	D	0.473	neutral	None	None	None	None	I
Q/V	0.2732	likely_benign	0.3369	benign	0.003	Stabilizing	0.543	D	0.525	neutral	None	None	None	None	I
Q/W	0.6161	likely_pathogenic	0.7717	pathogenic	-0.173	Destabilizing	0.995	D	0.533	neutral	None	None	None	None	I
Q/Y	0.5131	ambiguous	0.6167	pathogenic	0.047	Stabilizing	0.944	D	0.527	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.