TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22278	67057;67058;67059	chr2:178580547;178580546;178580545	chr2:179445274;179445273;179445272
N2AB	20637	62134;62135;62136	chr2:178580547;178580546;178580545	chr2:179445274;179445273;179445272
N2A	19710	59353;59354;59355	chr2:178580547;178580546;178580545	chr2:179445274;179445273;179445272
N2B	13213	39862;39863;39864	chr2:178580547;178580546;178580545	chr2:179445274;179445273;179445272
Novex-1	13338	40237;40238;40239	chr2:178580547;178580546;178580545	chr2:179445274;179445273;179445272
Novex-2	13405	40438;40439;40440	chr2:178580547;178580546;178580545	chr2:179445274;179445273;179445272
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-126
• Domain position: 14
• Structural Position: 26
• Q(SASA): 0.3531
• 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
T/I	rs1449367862	-0.084	0.994	N	0.747	0.395	0.479286488449	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
T/I	rs1449367862	-0.084	0.994	N	0.747	0.395	0.479286488449	gnomAD-4.0.0	7.96889E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.77017E-05	0	8.58595E-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
T/A	0.181	likely_benign	0.1487	benign	-0.826	Destabilizing	0.958	D	0.446	neutral	N	0.491438555	None	None	I
T/C	0.7185	likely_pathogenic	0.631	pathogenic	-0.557	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
T/D	0.784	likely_pathogenic	0.7057	pathogenic	-0.599	Destabilizing	0.995	D	0.656	neutral	None	None	None	None	I
T/E	0.7178	likely_pathogenic	0.6317	pathogenic	-0.579	Destabilizing	0.991	D	0.659	neutral	None	None	None	None	I
T/F	0.7253	likely_pathogenic	0.6177	pathogenic	-0.743	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	I
T/G	0.5506	ambiguous	0.4678	ambiguous	-1.117	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	I
T/H	0.696	likely_pathogenic	0.5975	pathogenic	-1.361	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
T/I	0.5391	ambiguous	0.4571	ambiguous	-0.134	Destabilizing	0.994	D	0.747	deleterious	N	0.471722909	None	None	I
T/K	0.683	likely_pathogenic	0.6242	pathogenic	-0.94	Destabilizing	0.991	D	0.665	neutral	None	None	None	None	I
T/L	0.3618	ambiguous	0.29	benign	-0.134	Destabilizing	0.968	D	0.559	neutral	None	None	None	None	I
T/M	0.2164	likely_benign	0.1758	benign	0.155	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
T/N	0.3377	likely_benign	0.2725	benign	-0.922	Destabilizing	0.994	D	0.716	prob.delet.	N	0.508984166	None	None	I
T/P	0.216	likely_benign	0.1688	benign	-0.332	Destabilizing	0.067	N	0.329	neutral	N	0.459960855	None	None	I
T/Q	0.5884	likely_pathogenic	0.5012	ambiguous	-1.06	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	I
T/R	0.6827	likely_pathogenic	0.6063	pathogenic	-0.687	Destabilizing	0.995	D	0.74	deleterious	None	None	None	None	I
T/S	0.2096	likely_benign	0.1675	benign	-1.16	Destabilizing	0.958	D	0.429	neutral	N	0.42796308	None	None	I
T/V	0.3637	ambiguous	0.3089	benign	-0.332	Destabilizing	0.984	D	0.511	neutral	None	None	None	None	I
T/W	0.9283	likely_pathogenic	0.8757	pathogenic	-0.701	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
T/Y	0.7576	likely_pathogenic	0.6673	pathogenic	-0.485	Destabilizing	0.998	D	0.763	deleterious	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.