TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23691	71296;71297;71298	chr2:178575061;178575060;178575059	chr2:179439788;179439787;179439786
N2AB	22050	66373;66374;66375	chr2:178575061;178575060;178575059	chr2:179439788;179439787;179439786
N2A	21123	63592;63593;63594	chr2:178575061;178575060;178575059	chr2:179439788;179439787;179439786
N2B	14626	44101;44102;44103	chr2:178575061;178575060;178575059	chr2:179439788;179439787;179439786
Novex-1	14751	44476;44477;44478	chr2:178575061;178575060;178575059	chr2:179439788;179439787;179439786
Novex-2	14818	44677;44678;44679	chr2:178575061;178575060;178575059	chr2:179439788;179439787;179439786
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-130
• Domain position: 55
• Structural Position: 138
• Q(SASA): 0.0975
• 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/S	rs1358981791	None	1.0	D	0.87	0.874	0.864153557662	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/S	rs1358981791	None	1.0	D	0.87	0.874	0.864153557662	gnomAD-4.0.0	3.71911E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08644E-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
L/A	0.9591	likely_pathogenic	0.9684	pathogenic	-2.653	Highly Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
L/C	0.8862	likely_pathogenic	0.9137	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.479	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9978	pathogenic	-3.144	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/F	0.3297	likely_benign	0.4644	ambiguous	-1.682	Destabilizing	0.64	D	0.487	neutral	N	0.504910945	None	None	N
L/G	0.9933	likely_pathogenic	0.9947	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/H	0.9865	likely_pathogenic	0.9903	pathogenic	-3.141	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/I	0.1586	likely_benign	0.1897	benign	-0.783	Destabilizing	0.996	D	0.681	prob.neutral	N	0.511632441	None	None	N
L/K	0.9936	likely_pathogenic	0.9941	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/M	0.2634	likely_benign	0.2997	benign	-1.021	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
L/N	0.9978	likely_pathogenic	0.9983	pathogenic	-3.027	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/P	0.9972	likely_pathogenic	0.9975	pathogenic	-1.398	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/Q	0.9853	likely_pathogenic	0.9873	pathogenic	-2.61	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/R	0.9831	likely_pathogenic	0.985	pathogenic	-2.424	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/S	0.9951	likely_pathogenic	0.9964	pathogenic	-3.558	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.554009924	None	None	N
L/T	0.9808	likely_pathogenic	0.9854	pathogenic	-3.044	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/V	0.2523	likely_benign	0.2988	benign	-1.398	Destabilizing	0.996	D	0.699	prob.neutral	N	0.516191571	None	None	N
L/W	0.8726	likely_pathogenic	0.9093	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/Y	0.9234	likely_pathogenic	0.9512	pathogenic	-1.869	Destabilizing	0.998	D	0.837	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.