TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22360	67303;67304;67305	chr2:178580209;178580208;178580207	chr2:179444936;179444935;179444934
N2AB	20719	62380;62381;62382	chr2:178580209;178580208;178580207	chr2:179444936;179444935;179444934
N2A	19792	59599;59600;59601	chr2:178580209;178580208;178580207	chr2:179444936;179444935;179444934
N2B	13295	40108;40109;40110	chr2:178580209;178580208;178580207	chr2:179444936;179444935;179444934
Novex-1	13420	40483;40484;40485	chr2:178580209;178580208;178580207	chr2:179444936;179444935;179444934
Novex-2	13487	40684;40685;40686	chr2:178580209;178580208;178580207	chr2:179444936;179444935;179444934
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-50
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5946
• Predicted PPI site: I

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
N/H	None	None	0.999	N	0.655	0.501	0.322230723748	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
N/A	0.2879	likely_benign	0.2382	benign	-0.269	Destabilizing	0.992	D	0.567	neutral	None	None	None	None	I
N/C	0.3671	ambiguous	0.3057	benign	0.25	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
N/D	0.1745	likely_benign	0.1521	benign	0.134	Stabilizing	0.998	D	0.562	neutral	N	0.517849657	None	None	I
N/E	0.492	ambiguous	0.4293	ambiguous	0.1	Stabilizing	0.999	D	0.604	neutral	None	None	None	None	I
N/F	0.6263	likely_pathogenic	0.5646	pathogenic	-0.637	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	I
N/G	0.2961	likely_benign	0.267	benign	-0.439	Destabilizing	0.996	D	0.49	neutral	None	None	None	None	I
N/H	0.1466	likely_benign	0.1347	benign	-0.418	Destabilizing	0.999	D	0.655	neutral	N	0.489684666	None	None	I
N/I	0.4719	ambiguous	0.405	ambiguous	0.087	Stabilizing	0.994	D	0.731	prob.delet.	N	0.520284088	None	None	I
N/K	0.3989	ambiguous	0.3413	ambiguous	0.062	Stabilizing	0.994	D	0.585	neutral	N	0.50388307	None	None	I
N/L	0.361	ambiguous	0.3195	benign	0.087	Stabilizing	0.983	D	0.574	neutral	None	None	None	None	I
N/M	0.4404	ambiguous	0.3964	ambiguous	0.288	Stabilizing	0.96	D	0.41	neutral	None	None	None	None	I
N/P	0.8482	likely_pathogenic	0.7916	pathogenic	-0.005	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/Q	0.3984	ambiguous	0.351	ambiguous	-0.401	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
N/R	0.4301	ambiguous	0.3833	ambiguous	0.121	Stabilizing	0.999	D	0.652	neutral	None	None	None	None	I
N/S	0.1126	likely_benign	0.1065	benign	-0.183	Destabilizing	0.994	D	0.488	neutral	N	0.505403222	None	None	I
N/T	0.2269	likely_benign	0.189	benign	-0.077	Destabilizing	0.994	D	0.585	neutral	N	0.490000607	None	None	I
N/V	0.45	ambiguous	0.3739	ambiguous	-0.005	Destabilizing	0.995	D	0.633	neutral	None	None	None	None	I
N/W	0.836	likely_pathogenic	0.8144	pathogenic	-0.646	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
N/Y	0.2512	likely_benign	0.2248	benign	-0.372	Destabilizing	0.999	D	0.743	deleterious	D	0.539148812	None	None	I

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.