TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15637	47134;47135;47136	chr2:178618641;178618640;178618639	chr2:179483368;179483367;179483366
N2AB	13996	42211;42212;42213	chr2:178618641;178618640;178618639	chr2:179483368;179483367;179483366
N2A	13069	39430;39431;39432	chr2:178618641;178618640;178618639	chr2:179483368;179483367;179483366
N2B	6572	19939;19940;19941	chr2:178618641;178618640;178618639	chr2:179483368;179483367;179483366
Novex-1	6697	20314;20315;20316	chr2:178618641;178618640;178618639	chr2:179483368;179483367;179483366
Novex-2	6764	20515;20516;20517	chr2:178618641;178618640;178618639	chr2:179483368;179483367;179483366
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-108
• Domain position: 70
• Structural Position: 156
• Q(SASA): 0.0931
• 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/L	rs1029825916	None	0.025	N	0.408	0.063	0.158396225186	gnomAD-4.0.0	2.73894E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79993E-06	0	3.31774E-05
I/T	None	None	0.124	N	0.715	0.255	0.515659482774	gnomAD-4.0.0	1.59407E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86325E-06	0	0
I/V	None	None	None	N	0.329	0.053	0.107399877778	gnomAD-4.0.0	1.36947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79993E-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
I/A	0.5985	likely_pathogenic	0.7115	pathogenic	-2.652	Highly Destabilizing	0.072	N	0.721	prob.delet.	None	None	None	None	N
I/C	0.8536	likely_pathogenic	0.8908	pathogenic	-1.575	Destabilizing	0.909	D	0.781	deleterious	None	None	None	None	N
I/D	0.9951	likely_pathogenic	0.9966	pathogenic	-3.391	Highly Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
I/E	0.9854	likely_pathogenic	0.9886	pathogenic	-3.089	Highly Destabilizing	0.726	D	0.822	deleterious	None	None	None	None	N
I/F	0.4055	ambiguous	0.4672	ambiguous	-1.667	Destabilizing	0.497	N	0.687	prob.neutral	N	0.453420042	None	None	N
I/G	0.9271	likely_pathogenic	0.9562	pathogenic	-3.217	Highly Destabilizing	0.726	D	0.815	deleterious	None	None	None	None	N
I/H	0.9829	likely_pathogenic	0.9869	pathogenic	-2.907	Highly Destabilizing	0.968	D	0.855	deleterious	None	None	None	None	N
I/K	0.9779	likely_pathogenic	0.9795	pathogenic	-2.04	Highly Destabilizing	0.726	D	0.826	deleterious	None	None	None	None	N
I/L	0.1817	likely_benign	0.2055	benign	-0.95	Destabilizing	0.025	N	0.408	neutral	N	0.435294528	None	None	N
I/M	0.1819	likely_benign	0.2069	benign	-0.917	Destabilizing	0.497	N	0.668	neutral	N	0.455541523	None	None	N
I/N	0.9483	likely_pathogenic	0.9558	pathogenic	-2.697	Highly Destabilizing	0.859	D	0.847	deleterious	N	0.457109294	None	None	N
I/P	0.9824	likely_pathogenic	0.9872	pathogenic	-1.509	Destabilizing	0.89	D	0.846	deleterious	None	None	None	None	N
I/Q	0.9722	likely_pathogenic	0.9773	pathogenic	-2.396	Highly Destabilizing	0.89	D	0.845	deleterious	None	None	None	None	N
I/R	0.9589	likely_pathogenic	0.9648	pathogenic	-2.035	Highly Destabilizing	0.726	D	0.846	deleterious	None	None	None	None	N
I/S	0.8891	likely_pathogenic	0.9192	pathogenic	-3.205	Highly Destabilizing	0.497	N	0.795	deleterious	N	0.456486004	None	None	N
I/T	0.6254	likely_pathogenic	0.7211	pathogenic	-2.755	Highly Destabilizing	0.124	N	0.715	prob.delet.	N	0.455541523	None	None	N
I/V	0.0656	likely_benign	0.0792	benign	-1.509	Destabilizing	None	N	0.329	neutral	N	0.394513697	None	None	N
I/W	0.975	likely_pathogenic	0.981	pathogenic	-2.11	Highly Destabilizing	0.968	D	0.841	deleterious	None	None	None	None	N
I/Y	0.9136	likely_pathogenic	0.9261	pathogenic	-1.851	Destabilizing	0.726	D	0.773	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.