TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31423	94492;94493;94494	chr2:178547258;178547257;178547256	chr2:179411985;179411984;179411983
N2AB	29782	89569;89570;89571	chr2:178547258;178547257;178547256	chr2:179411985;179411984;179411983
N2A	28855	86788;86789;86790	chr2:178547258;178547257;178547256	chr2:179411985;179411984;179411983
N2B	22358	67297;67298;67299	chr2:178547258;178547257;178547256	chr2:179411985;179411984;179411983
Novex-1	22483	67672;67673;67674	chr2:178547258;178547257;178547256	chr2:179411985;179411984;179411983
Novex-2	22550	67873;67874;67875	chr2:178547258;178547257;178547256	chr2:179411985;179411984;179411983
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-117
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.661
• 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
N/H	rs751814511	-0.823	0.859	N	0.491	0.282	0.247872288689	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
N/H	rs751814511	-0.823	0.859	N	0.491	0.282	0.247872288689	gnomAD-4.0.0	1.59153E-06	None	None	None	None	I	None	0	0	None	0	2.77346E-05	None	0	0	0	0	0
N/K	rs1387191410	0.406	0.22	N	0.455	0.133	0.16115917748	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
N/K	rs1387191410	0.406	0.22	N	0.455	0.133	0.16115917748	gnomAD-4.0.0	1.59148E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85884E-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
N/A	0.1682	likely_benign	0.19	benign	-0.642	Destabilizing	0.072	N	0.439	neutral	None	None	None	None	I
N/C	0.2734	likely_benign	0.2965	benign	0.149	Stabilizing	0.909	D	0.541	neutral	None	None	None	None	I
N/D	0.1137	likely_benign	0.1311	benign	-0.751	Destabilizing	0.22	N	0.5	neutral	N	0.399366261	None	None	I
N/E	0.3355	likely_benign	0.3942	ambiguous	-0.777	Destabilizing	0.272	N	0.451	neutral	None	None	None	None	I
N/F	0.4227	ambiguous	0.5013	ambiguous	-1.085	Destabilizing	0.726	D	0.555	neutral	None	None	None	None	I
N/G	0.1861	likely_benign	0.1984	benign	-0.807	Destabilizing	0.072	N	0.441	neutral	None	None	None	None	I
N/H	0.116	likely_benign	0.132	benign	-0.933	Destabilizing	0.859	D	0.491	neutral	N	0.501474696	None	None	I
N/I	0.3238	likely_benign	0.3779	ambiguous	-0.281	Destabilizing	0.331	N	0.544	neutral	N	0.500655215	None	None	I
N/K	0.3702	ambiguous	0.4609	ambiguous	0.008	Stabilizing	0.22	N	0.455	neutral	N	0.516846793	None	None	I
N/L	0.2327	likely_benign	0.2499	benign	-0.281	Destabilizing	0.157	N	0.493	neutral	None	None	None	None	I
N/M	0.2869	likely_benign	0.3164	benign	0.456	Stabilizing	0.909	D	0.526	neutral	None	None	None	None	I
N/P	0.8092	likely_pathogenic	0.795	pathogenic	-0.378	Destabilizing	0.726	D	0.527	neutral	None	None	None	None	I
N/Q	0.307	likely_benign	0.3504	ambiguous	-0.77	Destabilizing	0.726	D	0.476	neutral	None	None	None	None	I
N/R	0.403	ambiguous	0.4829	ambiguous	0.209	Stabilizing	0.567	D	0.457	neutral	None	None	None	None	I
N/S	0.0625	likely_benign	0.0638	benign	-0.346	Destabilizing	0.002	N	0.079	neutral	N	0.454083394	None	None	I
N/T	0.0928	likely_benign	0.0921	benign	-0.24	Destabilizing	None	N	0.081	neutral	N	0.467393834	None	None	I
N/V	0.2518	likely_benign	0.277	benign	-0.378	Destabilizing	0.157	N	0.481	neutral	None	None	None	None	I
N/W	0.739	likely_pathogenic	0.7899	pathogenic	-0.972	Destabilizing	0.968	D	0.673	neutral	None	None	None	None	I
N/Y	0.1819	likely_benign	0.2227	benign	-0.699	Destabilizing	0.667	D	0.541	neutral	N	0.48255096	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.