TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14870	44833;44834;44835	chr2:178624672;178624671;178624670	chr2:179489399;179489398;179489397
N2AB	13229	39910;39911;39912	chr2:178624672;178624671;178624670	chr2:179489399;179489398;179489397
N2A	12302	37129;37130;37131	chr2:178624672;178624671;178624670	chr2:179489399;179489398;179489397
N2B	5805	17638;17639;17640	chr2:178624672;178624671;178624670	chr2:179489399;179489398;179489397
Novex-1	5930	18013;18014;18015	chr2:178624672;178624671;178624670	chr2:179489399;179489398;179489397
Novex-2	5997	18214;18215;18216	chr2:178624672;178624671;178624670	chr2:179489399;179489398;179489397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-100
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1474
• 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/E	None	None	0.994	D	0.833	0.37	0.324161360171	gnomAD-4.0.0	2.40067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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	0.7638	likely_pathogenic	0.7936	pathogenic	-0.893	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/D	0.9819	likely_pathogenic	0.9783	pathogenic	-1.496	Destabilizing	0.998	D	0.846	deleterious	None	None	None	None	N
A/E	0.9659	likely_pathogenic	0.9637	pathogenic	-1.467	Destabilizing	0.994	D	0.833	deleterious	D	0.550446332	None	None	N
A/F	0.915	likely_pathogenic	0.9112	pathogenic	-0.957	Destabilizing	0.991	D	0.869	deleterious	None	None	None	None	N
A/G	0.4516	ambiguous	0.4629	ambiguous	-1.352	Destabilizing	0.979	D	0.641	neutral	N	0.436168072	None	None	N
A/H	0.9816	likely_pathogenic	0.9808	pathogenic	-1.554	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/I	0.7097	likely_pathogenic	0.7087	pathogenic	-0.254	Destabilizing	0.938	D	0.752	deleterious	None	None	None	None	N
A/K	0.9869	likely_pathogenic	0.9854	pathogenic	-1.423	Destabilizing	0.995	D	0.841	deleterious	None	None	None	None	N
A/L	0.6422	likely_pathogenic	0.6722	pathogenic	-0.254	Destabilizing	0.938	D	0.671	neutral	None	None	None	None	N
A/M	0.7463	likely_pathogenic	0.757	pathogenic	-0.164	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
A/N	0.9662	likely_pathogenic	0.9665	pathogenic	-1.213	Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
A/P	0.9779	likely_pathogenic	0.9769	pathogenic	-0.468	Destabilizing	0.998	D	0.863	deleterious	D	0.550446332	None	None	N
A/Q	0.9581	likely_pathogenic	0.9576	pathogenic	-1.281	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
A/R	0.9648	likely_pathogenic	0.961	pathogenic	-1.114	Destabilizing	0.995	D	0.859	deleterious	None	None	None	None	N
A/S	0.355	ambiguous	0.3684	ambiguous	-1.584	Destabilizing	0.979	D	0.639	neutral	N	0.466766058	None	None	N
A/T	0.3744	ambiguous	0.383	ambiguous	-1.451	Destabilizing	0.958	D	0.667	neutral	N	0.383080786	None	None	N
A/V	0.3312	likely_benign	0.3199	benign	-0.468	Destabilizing	0.142	N	0.354	neutral	N	0.349195582	None	None	N
A/W	0.9943	likely_pathogenic	0.994	pathogenic	-1.424	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/Y	0.9727	likely_pathogenic	0.9716	pathogenic	-0.984	Destabilizing	0.995	D	0.876	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.