TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20267	61024;61025;61026	chr2:178590926;178590925;178590924	chr2:179455653;179455652;179455651
N2AB	18626	56101;56102;56103	chr2:178590926;178590925;178590924	chr2:179455653;179455652;179455651
N2A	17699	53320;53321;53322	chr2:178590926;178590925;178590924	chr2:179455653;179455652;179455651
N2B	11202	33829;33830;33831	chr2:178590926;178590925;178590924	chr2:179455653;179455652;179455651
Novex-1	11327	34204;34205;34206	chr2:178590926;178590925;178590924	chr2:179455653;179455652;179455651
Novex-2	11394	34405;34406;34407	chr2:178590926;178590925;178590924	chr2:179455653;179455652;179455651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-34
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.0541
• 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
H/R	rs2050075865	None	0.93	N	0.36	0.218	0.292787519742	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
H/R	rs2050075865	None	0.93	N	0.36	0.218	0.292787519742	gnomAD-4.0.0	1.31508E-05	None	None	None	None	N	None	4.82649E-05	0	None	0	0	None	0	0	0	0	0
H/Y	None	None	0.006	N	0.252	0.172	0.198526703765	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
H/A	0.6616	likely_pathogenic	0.6789	pathogenic	0.48	Stabilizing	0.008	N	0.471	neutral	None	None	None	None	N
H/C	0.4066	ambiguous	0.4405	ambiguous	0.729	Stabilizing	0.985	D	0.615	neutral	None	None	None	None	N
H/D	0.4435	ambiguous	0.4646	ambiguous	-0.184	Destabilizing	0.93	D	0.429	neutral	N	0.444132972	None	None	N
H/E	0.616	likely_pathogenic	0.6385	pathogenic	-0.162	Destabilizing	0.712	D	0.388	neutral	None	None	None	None	N
H/F	0.4753	ambiguous	0.4491	ambiguous	1.155	Stabilizing	0.813	D	0.429	neutral	None	None	None	None	N
H/G	0.6978	likely_pathogenic	0.7133	pathogenic	0.222	Stabilizing	0.553	D	0.499	neutral	None	None	None	None	N
H/I	0.6844	likely_pathogenic	0.6879	pathogenic	1.132	Stabilizing	0.897	D	0.608	neutral	None	None	None	None	N
H/K	0.6894	likely_pathogenic	0.7273	pathogenic	0.402	Stabilizing	0.712	D	0.467	neutral	None	None	None	None	N
H/L	0.2157	likely_benign	0.2248	benign	1.132	Stabilizing	0.483	N	0.525	neutral	N	0.502178411	None	None	N
H/M	0.6851	likely_pathogenic	0.6706	pathogenic	0.751	Stabilizing	0.995	D	0.594	neutral	None	None	None	None	N
H/N	0.1893	likely_benign	0.1903	benign	0.264	Stabilizing	0.791	D	0.493	neutral	N	0.455080684	None	None	N
H/P	0.2146	likely_benign	0.2285	benign	0.939	Stabilizing	0.93	D	0.64	neutral	N	0.466930877	None	None	N
H/Q	0.5117	ambiguous	0.5546	ambiguous	0.361	Stabilizing	0.93	D	0.418	neutral	N	0.489827976	None	None	N
H/R	0.4634	ambiguous	0.5335	ambiguous	-0.185	Destabilizing	0.93	D	0.36	neutral	N	0.513992915	None	None	N
H/S	0.5213	ambiguous	0.5185	ambiguous	0.436	Stabilizing	0.553	D	0.411	neutral	None	None	None	None	N
H/T	0.6792	likely_pathogenic	0.6867	pathogenic	0.556	Stabilizing	0.712	D	0.499	neutral	None	None	None	None	N
H/V	0.6145	likely_pathogenic	0.6287	pathogenic	0.939	Stabilizing	0.553	D	0.535	neutral	None	None	None	None	N
H/W	0.5181	ambiguous	0.5051	ambiguous	1.095	Stabilizing	0.985	D	0.619	neutral	None	None	None	None	N
H/Y	0.1321	likely_benign	0.1367	benign	1.342	Stabilizing	0.006	N	0.252	neutral	N	0.463796168	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.