TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5936	18031;18032;18033	chr2:178730727;178730726;178730725	chr2:179595454;179595453;179595452
N2AB	5619	17080;17081;17082	chr2:178730727;178730726;178730725	chr2:179595454;179595453;179595452
N2A	4692	14299;14300;14301	chr2:178730727;178730726;178730725	chr2:179595454;179595453;179595452
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-43
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1409
• Predicted PPI site: N

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
I/S	rs1365679296	-2.522	0.27	N	0.535	0.457	0.619501705969	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
I/S	rs1365679296	-2.522	0.27	N	0.535	0.457	0.619501705969	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
I/S	rs1365679296	-2.522	0.27	N	0.535	0.457	0.619501705969	gnomAD-4.0.0	1.23973E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.19703E-05	0
I/T	rs1365679296	-2.095	0.01	N	0.366	0.32	0.38225645794	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.29618E-04	0
I/T	rs1365679296	-2.095	0.01	N	0.366	0.32	0.38225645794	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/T	rs1365679296	-2.095	0.01	N	0.366	0.32	0.38225645794	gnomAD-4.0.0	1.8596E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54343E-06	0	0
I/V	rs72648945	-0.838	0.001	N	0.157	0.078	None	gnomAD-2.1.1	9.71E-05	None	None	None	None	N	None	8.29E-05	0	None	0	0	None	0	None	0	1.82271E-04	2.82725E-04
I/V	rs72648945	-0.838	0.001	N	0.157	0.078	None	gnomAD-3.1.2	9.2E-05	None	None	None	None	N	None	4.83E-05	6.55E-05	0	0	0	None	0	0	1.61689E-04	0	0
I/V	rs72648945	-0.838	0.001	N	0.157	0.078	None	gnomAD-4.0.0	1.17777E-04	None	None	None	None	N	None	5.34074E-05	3.33622E-05	None	0	0	None	0	3.29272E-04	1.44976E-04	0	1.76158E-04

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
I/A	0.2549	likely_benign	0.2604	benign	-1.909	Destabilizing	0.004	N	0.352	neutral	None	None	None	None	N
I/C	0.7473	likely_pathogenic	0.7621	pathogenic	-1.261	Destabilizing	0.981	D	0.668	neutral	None	None	None	None	N
I/D	0.9538	likely_pathogenic	0.9628	pathogenic	-1.083	Destabilizing	0.828	D	0.709	prob.delet.	None	None	None	None	N
I/E	0.9073	likely_pathogenic	0.9205	pathogenic	-0.926	Destabilizing	0.828	D	0.661	neutral	None	None	None	None	N
I/F	0.3976	ambiguous	0.4381	ambiguous	-0.98	Destabilizing	0.642	D	0.629	neutral	N	0.503578346	None	None	N
I/G	0.8059	likely_pathogenic	0.8251	pathogenic	-2.387	Highly Destabilizing	0.495	N	0.574	neutral	None	None	None	None	N
I/H	0.8692	likely_pathogenic	0.8873	pathogenic	-1.479	Destabilizing	0.981	D	0.701	prob.neutral	None	None	None	None	N
I/K	0.8129	likely_pathogenic	0.8456	pathogenic	-1.22	Destabilizing	0.704	D	0.667	neutral	None	None	None	None	N
I/L	0.1758	likely_benign	0.1778	benign	-0.589	Destabilizing	0.065	N	0.394	neutral	N	0.456552404	None	None	N
I/M	0.1313	likely_benign	0.1329	benign	-0.6	Destabilizing	0.927	D	0.627	neutral	N	0.507330728	None	None	N
I/N	0.7371	likely_pathogenic	0.7731	pathogenic	-1.326	Destabilizing	0.927	D	0.729	prob.delet.	N	0.481420146	None	None	N
I/P	0.9264	likely_pathogenic	0.9272	pathogenic	-1.002	Destabilizing	0.828	D	0.719	prob.delet.	None	None	None	None	N
I/Q	0.8057	likely_pathogenic	0.8273	pathogenic	-1.257	Destabilizing	0.981	D	0.725	prob.delet.	None	None	None	None	N
I/R	0.7037	likely_pathogenic	0.7403	pathogenic	-0.898	Destabilizing	0.944	D	0.733	prob.delet.	None	None	None	None	N
I/S	0.4349	ambiguous	0.4528	ambiguous	-2.146	Highly Destabilizing	0.27	N	0.535	neutral	N	0.469810351	None	None	N
I/T	0.1433	likely_benign	0.1475	benign	-1.836	Destabilizing	0.01	N	0.366	neutral	N	0.462982518	None	None	N
I/V	0.0737	likely_benign	0.076	benign	-1.002	Destabilizing	0.001	N	0.157	neutral	N	0.388844544	None	None	N
I/W	0.9185	likely_pathogenic	0.9249	pathogenic	-1.135	Destabilizing	0.995	D	0.694	prob.neutral	None	None	None	None	N
I/Y	0.8499	likely_pathogenic	0.8643	pathogenic	-0.872	Destabilizing	0.944	D	0.697	prob.neutral	None	None	None	None	N

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.