TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15924	47995;47996;47997	chr2:178617225;178617224;178617223	chr2:179481952;179481951;179481950
N2AB	14283	43072;43073;43074	chr2:178617225;178617224;178617223	chr2:179481952;179481951;179481950
N2A	13356	40291;40292;40293	chr2:178617225;178617224;178617223	chr2:179481952;179481951;179481950
N2B	6859	20800;20801;20802	chr2:178617225;178617224;178617223	chr2:179481952;179481951;179481950
Novex-1	6984	21175;21176;21177	chr2:178617225;178617224;178617223	chr2:179481952;179481951;179481950
Novex-2	7051	21376;21377;21378	chr2:178617225;178617224;178617223	chr2:179481952;179481951;179481950
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-3
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.1055
• 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
L/F	None	None	1.0	D	0.875	0.53	0.706036002137	gnomAD-4.0.0	7.16023E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.25191E-07	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
L/A	0.931	likely_pathogenic	0.9269	pathogenic	-2.601	Highly Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
L/C	0.932	likely_pathogenic	0.9292	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/D	0.9972	likely_pathogenic	0.9969	pathogenic	-2.661	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/E	0.9835	likely_pathogenic	0.9821	pathogenic	-2.55	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/F	0.7519	likely_pathogenic	0.7555	pathogenic	-1.921	Destabilizing	1.0	D	0.875	deleterious	D	0.76144295	None	None	N
L/G	0.9816	likely_pathogenic	0.9814	pathogenic	-3.042	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/H	0.9718	likely_pathogenic	0.9703	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/I	0.2808	likely_benign	0.276	benign	-1.376	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
L/K	0.9692	likely_pathogenic	0.966	pathogenic	-1.973	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/M	0.4135	ambiguous	0.4171	ambiguous	-1.393	Destabilizing	1.0	D	0.845	deleterious	D	0.645129669	None	None	N
L/N	0.9774	likely_pathogenic	0.9765	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/P	0.9803	likely_pathogenic	0.9773	pathogenic	-1.761	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/Q	0.9441	likely_pathogenic	0.9387	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/R	0.9487	likely_pathogenic	0.9434	pathogenic	-1.398	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/S	0.9823	likely_pathogenic	0.9807	pathogenic	-2.863	Highly Destabilizing	1.0	D	0.838	deleterious	D	0.812669685	None	None	N
L/T	0.9064	likely_pathogenic	0.9024	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/V	0.3721	ambiguous	0.3633	ambiguous	-1.761	Destabilizing	0.999	D	0.841	deleterious	D	0.605213304	None	None	N
L/W	0.9476	likely_pathogenic	0.95	pathogenic	-2.051	Highly Destabilizing	1.0	D	0.755	deleterious	D	0.812669685	None	None	N
L/Y	0.9698	likely_pathogenic	0.9709	pathogenic	-1.833	Destabilizing	1.0	D	0.812	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.