TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18112	54559;54560;54561	chr2:178604755;178604754;178604753	chr2:179469482;179469481;179469480
N2AB	16471	49636;49637;49638	chr2:178604755;178604754;178604753	chr2:179469482;179469481;179469480
N2A	15544	46855;46856;46857	chr2:178604755;178604754;178604753	chr2:179469482;179469481;179469480
N2B	9047	27364;27365;27366	chr2:178604755;178604754;178604753	chr2:179469482;179469481;179469480
Novex-1	9172	27739;27740;27741	chr2:178604755;178604754;178604753	chr2:179469482;179469481;179469480
Novex-2	9239	27940;27941;27942	chr2:178604755;178604754;178604753	chr2:179469482;179469481;179469480
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-19
• Domain position: 48
• Structural Position: 63
• Q(SASA): 0.361
• 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
A/G	None	None	0.012	N	0.303	0.081	0.0666544352282	gnomAD-4.0.0	1.59546E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86571E-06	0	0
A/T	None	None	None	N	0.212	0.065	0.0611884634855	gnomAD-4.0.0	1.36986E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80033E-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
A/C	0.3521	ambiguous	0.322	benign	-0.738	Destabilizing	0.356	N	0.293	neutral	None	None	None	None	N
A/D	0.2965	likely_benign	0.3093	benign	-1.177	Destabilizing	0.016	N	0.399	neutral	None	None	None	None	N
A/E	0.3206	likely_benign	0.3191	benign	-1.288	Destabilizing	0.012	N	0.358	neutral	N	0.419909318	None	None	N
A/F	0.3789	ambiguous	0.3908	ambiguous	-1.26	Destabilizing	0.072	N	0.469	neutral	None	None	None	None	N
A/G	0.1116	likely_benign	0.1055	benign	-1.069	Destabilizing	0.012	N	0.303	neutral	N	0.376331899	None	None	N
A/H	0.4723	ambiguous	0.4876	ambiguous	-1.233	Destabilizing	0.356	N	0.445	neutral	None	None	None	None	N
A/I	0.2728	likely_benign	0.275	benign	-0.656	Destabilizing	None	N	0.295	neutral	None	None	None	None	N
A/K	0.5697	likely_pathogenic	0.593	pathogenic	-1.22	Destabilizing	0.016	N	0.355	neutral	None	None	None	None	N
A/L	0.1818	likely_benign	0.1829	benign	-0.656	Destabilizing	0.002	N	0.341	neutral	None	None	None	None	N
A/M	0.1993	likely_benign	0.2057	benign	-0.43	Destabilizing	0.214	N	0.341	neutral	None	None	None	None	N
A/N	0.1907	likely_benign	0.2125	benign	-0.735	Destabilizing	0.038	N	0.395	neutral	None	None	None	None	N
A/P	0.2582	likely_benign	0.2299	benign	-0.704	Destabilizing	0.055	N	0.347	neutral	N	0.440343305	None	None	N
A/Q	0.3736	ambiguous	0.3887	ambiguous	-1.024	Destabilizing	0.072	N	0.37	neutral	None	None	None	None	N
A/R	0.5676	likely_pathogenic	0.5776	pathogenic	-0.727	Destabilizing	0.072	N	0.375	neutral	None	None	None	None	N
A/S	0.0714	likely_benign	0.0716	benign	-0.961	Destabilizing	None	N	0.21	neutral	N	0.384065948	None	None	N
A/T	0.0777	likely_benign	0.0806	benign	-1.003	Destabilizing	None	N	0.212	neutral	N	0.437399001	None	None	N
A/V	0.1482	likely_benign	0.141	benign	-0.704	Destabilizing	None	N	0.211	neutral	N	0.447999996	None	None	N
A/W	0.6542	likely_pathogenic	0.6352	pathogenic	-1.463	Destabilizing	0.864	D	0.435	neutral	None	None	None	None	N
A/Y	0.4216	ambiguous	0.4182	ambiguous	-1.147	Destabilizing	0.356	N	0.467	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.