TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6940	21043;21044;21045	chr2:178725386;178725385;178725384	chr2:179590113;179590112;179590111
N2AB	6623	20092;20093;20094	chr2:178725386;178725385;178725384	chr2:179590113;179590112;179590111
N2A	5696	17311;17312;17313	chr2:178725386;178725385;178725384	chr2:179590113;179590112;179590111
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-53
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.15
• 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/S	None	None	0.775	N	0.355	0.441	0.362361684037	gnomAD-4.0.0	1.67561E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.0051E-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	0.7586	likely_pathogenic	0.765	pathogenic	-1.178	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/D	0.9013	likely_pathogenic	0.9209	pathogenic	-1.842	Destabilizing	0.997	D	0.799	deleterious	D	0.545319283	None	None	N
A/E	0.9213	likely_pathogenic	0.9403	pathogenic	-1.794	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
A/F	0.9067	likely_pathogenic	0.9162	pathogenic	-1.068	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
A/G	0.2028	likely_benign	0.2067	benign	-1.512	Destabilizing	0.989	D	0.491	neutral	D	0.522188598	None	None	N
A/H	0.97	likely_pathogenic	0.9749	pathogenic	-1.773	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/I	0.7951	likely_pathogenic	0.8162	pathogenic	-0.291	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
A/K	0.9802	likely_pathogenic	0.9854	pathogenic	-1.43	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
A/L	0.7131	likely_pathogenic	0.7382	pathogenic	-0.291	Destabilizing	0.992	D	0.683	prob.neutral	None	None	None	None	N
A/M	0.749	likely_pathogenic	0.7711	pathogenic	-0.25	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
A/N	0.8829	likely_pathogenic	0.8954	pathogenic	-1.318	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
A/P	0.9848	likely_pathogenic	0.988	pathogenic	-0.536	Destabilizing	0.998	D	0.807	deleterious	D	0.527215028	None	None	N
A/Q	0.9256	likely_pathogenic	0.9409	pathogenic	-1.374	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
A/R	0.9651	likely_pathogenic	0.973	pathogenic	-1.188	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
A/S	0.2072	likely_benign	0.2132	benign	-1.721	Destabilizing	0.775	D	0.355	neutral	N	0.507589835	None	None	N
A/T	0.2735	likely_benign	0.2992	benign	-1.566	Destabilizing	0.733	D	0.36	neutral	N	0.507336346	None	None	N
A/V	0.4521	ambiguous	0.4869	ambiguous	-0.536	Destabilizing	0.989	D	0.565	neutral	N	0.496292301	None	None	N
A/W	0.9914	likely_pathogenic	0.9926	pathogenic	-1.569	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/Y	0.9621	likely_pathogenic	0.9654	pathogenic	-1.124	Destabilizing	1.0	D	0.859	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.