TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28483	85672;85673;85674	chr2:178560685;178560684;178560683	chr2:179425412;179425411;179425410
N2AB	26842	80749;80750;80751	chr2:178560685;178560684;178560683	chr2:179425412;179425411;179425410
N2A	25915	77968;77969;77970	chr2:178560685;178560684;178560683	chr2:179425412;179425411;179425410
N2B	19418	58477;58478;58479	chr2:178560685;178560684;178560683	chr2:179425412;179425411;179425410
Novex-1	19543	58852;58853;58854	chr2:178560685;178560684;178560683	chr2:179425412;179425411;179425410
Novex-2	19610	59053;59054;59055	chr2:178560685;178560684;178560683	chr2:179425412;179425411;179425410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-95
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2082
• 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/V	None	None	0.003	N	0.179	0.124	0.419461527279	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
I/A	0.688	likely_pathogenic	0.6685	pathogenic	-2.439	Highly Destabilizing	0.415	N	0.622	neutral	None	None	None	None	N
I/C	0.9062	likely_pathogenic	0.9027	pathogenic	-1.439	Destabilizing	0.989	D	0.74	deleterious	None	None	None	None	N
I/D	0.9793	likely_pathogenic	0.9818	pathogenic	-2.589	Highly Destabilizing	0.923	D	0.828	deleterious	None	None	None	None	N
I/E	0.9604	likely_pathogenic	0.9645	pathogenic	-2.491	Highly Destabilizing	0.923	D	0.833	deleterious	None	None	None	None	N
I/F	0.6979	likely_pathogenic	0.6784	pathogenic	-1.612	Destabilizing	0.901	D	0.709	prob.delet.	D	0.535399376	None	None	N
I/G	0.9558	likely_pathogenic	0.958	pathogenic	-2.872	Highly Destabilizing	0.858	D	0.82	deleterious	None	None	None	None	N
I/H	0.9665	likely_pathogenic	0.9678	pathogenic	-2.273	Highly Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
I/K	0.9034	likely_pathogenic	0.9126	pathogenic	-1.875	Destabilizing	0.923	D	0.835	deleterious	None	None	None	None	N
I/L	0.3056	likely_benign	0.2881	benign	-1.235	Destabilizing	0.19	N	0.443	neutral	N	0.499342223	None	None	N
I/M	0.2799	likely_benign	0.2682	benign	-0.869	Destabilizing	0.959	D	0.673	neutral	D	0.556038526	None	None	N
I/N	0.823	likely_pathogenic	0.8549	pathogenic	-1.827	Destabilizing	0.901	D	0.837	deleterious	D	0.530554438	None	None	N
I/P	0.8566	likely_pathogenic	0.8696	pathogenic	-1.613	Destabilizing	0.961	D	0.842	deleterious	None	None	None	None	N
I/Q	0.9431	likely_pathogenic	0.9459	pathogenic	-1.901	Destabilizing	0.923	D	0.845	deleterious	None	None	None	None	N
I/R	0.8511	likely_pathogenic	0.8657	pathogenic	-1.326	Destabilizing	0.923	D	0.85	deleterious	None	None	None	None	N
I/S	0.767	likely_pathogenic	0.7813	pathogenic	-2.421	Highly Destabilizing	0.075	N	0.479	neutral	D	0.54493571	None	None	N
I/T	0.3416	ambiguous	0.3311	benign	-2.208	Highly Destabilizing	0.565	D	0.695	prob.neutral	D	0.52979397	None	None	N
I/V	0.0859	likely_benign	0.079	benign	-1.613	Destabilizing	0.003	N	0.179	neutral	N	0.503669639	None	None	N
I/W	0.9833	likely_pathogenic	0.9792	pathogenic	-1.91	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
I/Y	0.94	likely_pathogenic	0.9425	pathogenic	-1.702	Destabilizing	0.961	D	0.777	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.