TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2330	7213;7214;7215	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001
N2AB	2330	7213;7214;7215	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001
N2A	2330	7213;7214;7215	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001
N2B	2284	7075;7076;7077	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001
Novex-1	2284	7075;7076;7077	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001
Novex-2	2284	7075;7076;7077	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001
Novex-3	2330	7213;7214;7215	chr2:178774276;178774275;178774274	chr2:179639003;179639002;179639001

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-12
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.4776
• 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
K/N	None	None	0.993	N	0.569	0.15	0.124217242631	gnomAD-4.0.0	2.05222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79861E-06	0	1.65574E-05

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
K/A	0.2681	likely_benign	0.25	benign	0.059	Stabilizing	0.983	D	0.475	neutral	None	None	None	None	N
K/C	0.7776	likely_pathogenic	0.758	pathogenic	-0.057	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/D	0.548	ambiguous	0.5204	ambiguous	-0.062	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
K/E	0.1492	likely_benign	0.1412	benign	-0.055	Destabilizing	0.977	D	0.405	neutral	N	0.422456795	None	None	N
K/F	0.7827	likely_pathogenic	0.7507	pathogenic	-0.104	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/G	0.4013	ambiguous	0.3865	ambiguous	-0.146	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	N
K/H	0.3958	ambiguous	0.3694	ambiguous	-0.391	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	N
K/I	0.352	ambiguous	0.3184	benign	0.523	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
K/L	0.329	likely_benign	0.3028	benign	0.523	Stabilizing	0.995	D	0.522	neutral	None	None	None	None	N
K/M	0.247	likely_benign	0.2308	benign	0.265	Stabilizing	1.0	D	0.64	neutral	N	0.417163264	None	None	N
K/N	0.4578	ambiguous	0.4263	ambiguous	0.324	Stabilizing	0.993	D	0.569	neutral	N	0.453297783	None	None	N
K/P	0.5154	ambiguous	0.4902	ambiguous	0.396	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
K/Q	0.1507	likely_benign	0.1433	benign	0.15	Stabilizing	0.993	D	0.563	neutral	N	0.443395995	None	None	N
K/R	0.0833	likely_benign	0.0816	benign	0.009	Stabilizing	0.235	N	0.239	neutral	N	0.44490331	None	None	N
K/S	0.3818	ambiguous	0.3623	ambiguous	-0.109	Destabilizing	0.983	D	0.46	neutral	None	None	None	None	N
K/T	0.2035	likely_benign	0.1882	benign	0.039	Stabilizing	0.997	D	0.571	neutral	N	0.439175202	None	None	N
K/V	0.297	likely_benign	0.2753	benign	0.396	Stabilizing	0.998	D	0.63	neutral	None	None	None	None	N
K/W	0.747	likely_pathogenic	0.7324	pathogenic	-0.14	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/Y	0.6632	likely_pathogenic	0.6337	pathogenic	0.201	Stabilizing	0.999	D	0.658	neutral	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.