TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9077	27454;27455;27456	chr2:178712796;178712795;178712794	chr2:179577523;179577522;179577521
N2AB	8760	26503;26504;26505	chr2:178712796;178712795;178712794	chr2:179577523;179577522;179577521
N2A	7833	23722;23723;23724	chr2:178712796;178712795;178712794	chr2:179577523;179577522;179577521
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-76
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2849
• 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
E/V	rs1184239889	-0.218	0.733	N	0.449	0.304	0.552408913969	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	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
E/A	0.3162	likely_benign	0.3252	benign	-0.921	Destabilizing	0.989	D	0.551	neutral	N	0.495745642	None	None	N
E/C	0.9339	likely_pathogenic	0.939	pathogenic	-0.647	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/D	0.4702	ambiguous	0.4467	ambiguous	-1.484	Destabilizing	0.998	D	0.497	neutral	N	0.509686068	None	None	N
E/F	0.8437	likely_pathogenic	0.8429	pathogenic	-0.538	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
E/G	0.4983	ambiguous	0.5179	ambiguous	-1.336	Destabilizing	0.999	D	0.696	prob.neutral	N	0.521206958	None	None	N
E/H	0.5918	likely_pathogenic	0.5985	pathogenic	-0.974	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/I	0.4788	ambiguous	0.4778	ambiguous	0.231	Stabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
E/K	0.2984	likely_benign	0.3109	benign	-1.116	Destabilizing	0.998	D	0.519	neutral	N	0.48570601	None	None	N
E/L	0.5295	ambiguous	0.5392	ambiguous	0.231	Stabilizing	0.983	D	0.672	neutral	None	None	None	None	N
E/M	0.5545	ambiguous	0.5572	ambiguous	0.83	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/N	0.614	likely_pathogenic	0.5932	pathogenic	-1.493	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/P	0.9909	likely_pathogenic	0.9928	pathogenic	-0.132	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Q	0.1555	likely_benign	0.1617	benign	-1.271	Destabilizing	0.999	D	0.627	neutral	N	0.514319068	None	None	N
E/R	0.3935	ambiguous	0.4123	ambiguous	-0.972	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/S	0.4208	ambiguous	0.4025	ambiguous	-1.965	Destabilizing	0.996	D	0.553	neutral	None	None	None	None	N
E/T	0.3794	ambiguous	0.3684	ambiguous	-1.606	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
E/V	0.2819	likely_benign	0.2864	benign	-0.132	Destabilizing	0.733	D	0.449	neutral	N	0.496482668	None	None	N
E/W	0.9378	likely_pathogenic	0.9441	pathogenic	-0.487	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Y	0.7735	likely_pathogenic	0.7816	pathogenic	-0.339	Destabilizing	1.0	D	0.756	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.