TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18933	57022;57023;57024	chr2:178598913;178598912;178598911	chr2:179463640;179463639;179463638
N2AB	17292	52099;52100;52101	chr2:178598913;178598912;178598911	chr2:179463640;179463639;179463638
N2A	16365	49318;49319;49320	chr2:178598913;178598912;178598911	chr2:179463640;179463639;179463638
N2B	9868	29827;29828;29829	chr2:178598913;178598912;178598911	chr2:179463640;179463639;179463638
Novex-1	9993	30202;30203;30204	chr2:178598913;178598912;178598911	chr2:179463640;179463639;179463638
Novex-2	10060	30403;30404;30405	chr2:178598913;178598912;178598911	chr2:179463640;179463639;179463638
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-25
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.2333
• 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
R/G	rs780239769	-1.723	1.0	N	0.708	0.352	0.593343648767	gnomAD-4.0.0	3.42228E-06	None	None	None	None	N	None	2.99043E-05	0	None	0	5.05587E-05	None	0	0	1.7993E-06	0	0
R/I	None	None	1.0	N	0.765	0.38	0.672838725995	gnomAD-4.0.0	1.59263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86015E-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
R/A	0.9657	likely_pathogenic	0.9302	pathogenic	-0.736	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
R/C	0.8557	likely_pathogenic	0.7988	pathogenic	-0.654	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
R/D	0.9932	likely_pathogenic	0.9895	pathogenic	-0.034	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
R/E	0.9667	likely_pathogenic	0.9386	pathogenic	0.134	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	N
R/F	0.985	likely_pathogenic	0.9762	pathogenic	-0.31	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/G	0.9674	likely_pathogenic	0.9413	pathogenic	-1.086	Destabilizing	1.0	D	0.708	prob.delet.	N	0.469571586	None	None	N
R/H	0.6825	likely_pathogenic	0.6139	pathogenic	-1.431	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
R/I	0.9223	likely_pathogenic	0.8661	pathogenic	0.221	Stabilizing	1.0	D	0.765	deleterious	N	0.514363848	None	None	N
R/K	0.3085	likely_benign	0.2686	benign	-0.607	Destabilizing	0.997	D	0.509	neutral	N	0.474440023	None	None	N
R/L	0.8627	likely_pathogenic	0.8045	pathogenic	0.221	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
R/M	0.917	likely_pathogenic	0.8618	pathogenic	-0.313	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
R/N	0.9862	likely_pathogenic	0.9799	pathogenic	-0.305	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/P	0.8923	likely_pathogenic	0.8621	pathogenic	-0.077	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/Q	0.6143	likely_pathogenic	0.5131	ambiguous	-0.308	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
R/S	0.991	likely_pathogenic	0.9839	pathogenic	-0.997	Destabilizing	1.0	D	0.77	deleterious	N	0.501682552	None	None	N
R/T	0.9555	likely_pathogenic	0.9275	pathogenic	-0.626	Destabilizing	1.0	D	0.763	deleterious	N	0.478613692	None	None	N
R/V	0.9228	likely_pathogenic	0.8781	pathogenic	-0.077	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
R/W	0.8643	likely_pathogenic	0.8301	pathogenic	0.013	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
R/Y	0.9535	likely_pathogenic	0.9388	pathogenic	0.265	Stabilizing	1.0	D	0.765	deleterious	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.