TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20151	60676;60677;60678	chr2:178591274;178591273;178591272	chr2:179456001;179456000;179455999
N2AB	18510	55753;55754;55755	chr2:178591274;178591273;178591272	chr2:179456001;179456000;179455999
N2A	17583	52972;52973;52974	chr2:178591274;178591273;178591272	chr2:179456001;179456000;179455999
N2B	11086	33481;33482;33483	chr2:178591274;178591273;178591272	chr2:179456001;179456000;179455999
Novex-1	11211	33856;33857;33858	chr2:178591274;178591273;178591272	chr2:179456001;179456000;179455999
Novex-2	11278	34057;34058;34059	chr2:178591274;178591273;178591272	chr2:179456001;179456000;179455999
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-120
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.0543
• 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/T	rs746925706	-2.288	0.117	N	0.683	0.295	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs746925706	-2.288	0.117	N	0.683	0.295	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs746925706	-2.288	0.117	N	0.683	0.295	None	gnomAD-4.0.0	6.57765E-06	None	None	None	None	N	None	2.41406E-05	0	None	0	0	None	0	0	0	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
I/A	0.9211	likely_pathogenic	0.9404	pathogenic	-2.225	Highly Destabilizing	0.067	N	0.617	neutral	None	None	None	None	N
I/C	0.9177	likely_pathogenic	0.9328	pathogenic	-1.734	Destabilizing	0.791	D	0.761	deleterious	None	None	None	None	N
I/D	0.9982	likely_pathogenic	0.9987	pathogenic	-2.403	Highly Destabilizing	0.791	D	0.823	deleterious	None	None	None	None	N
I/E	0.9939	likely_pathogenic	0.995	pathogenic	-2.237	Highly Destabilizing	0.555	D	0.802	deleterious	None	None	None	None	N
I/F	0.4199	ambiguous	0.5285	ambiguous	-1.362	Destabilizing	0.062	N	0.645	neutral	N	0.508349448	None	None	N
I/G	0.9849	likely_pathogenic	0.9894	pathogenic	-2.723	Highly Destabilizing	0.555	D	0.799	deleterious	None	None	None	None	N
I/H	0.9898	likely_pathogenic	0.9925	pathogenic	-2.159	Highly Destabilizing	0.935	D	0.841	deleterious	None	None	None	None	N
I/K	0.9869	likely_pathogenic	0.9892	pathogenic	-1.558	Destabilizing	0.262	N	0.801	deleterious	None	None	None	None	N
I/L	0.0657	likely_benign	0.0689	benign	-0.822	Destabilizing	None	N	0.261	neutral	N	0.387559252	None	None	N
I/M	0.1198	likely_benign	0.1386	benign	-0.881	Destabilizing	0.188	N	0.634	neutral	N	0.456959562	None	None	N
I/N	0.9771	likely_pathogenic	0.982	pathogenic	-1.765	Destabilizing	0.741	D	0.832	deleterious	N	0.475570796	None	None	N
I/P	0.9952	likely_pathogenic	0.9964	pathogenic	-1.267	Destabilizing	0.791	D	0.831	deleterious	None	None	None	None	N
I/Q	0.9844	likely_pathogenic	0.9871	pathogenic	-1.725	Destabilizing	0.791	D	0.833	deleterious	None	None	None	None	N
I/R	0.9818	likely_pathogenic	0.9852	pathogenic	-1.237	Destabilizing	0.555	D	0.82	deleterious	None	None	None	None	N
I/S	0.9804	likely_pathogenic	0.9857	pathogenic	-2.469	Highly Destabilizing	0.211	N	0.744	deleterious	N	0.475317306	None	None	N
I/T	0.9612	likely_pathogenic	0.9715	pathogenic	-2.16	Highly Destabilizing	0.117	N	0.683	prob.neutral	N	0.475063817	None	None	N
I/V	0.1351	likely_benign	0.161	benign	-1.267	Destabilizing	0.005	N	0.354	neutral	N	0.442161741	None	None	N
I/W	0.9776	likely_pathogenic	0.9843	pathogenic	-1.687	Destabilizing	0.935	D	0.835	deleterious	None	None	None	None	N
I/Y	0.9227	likely_pathogenic	0.9437	pathogenic	-1.385	Destabilizing	0.555	D	0.727	prob.delet.	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.