TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5698	17317;17318;17319	chr2:178731783;178731782;178731781	chr2:179596510;179596509;179596508
N2AB	5381	16366;16367;16368	chr2:178731783;178731782;178731781	chr2:179596510;179596509;179596508
N2A	4454	13585;13586;13587	chr2:178731783;178731782;178731781	chr2:179596510;179596509;179596508
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-40
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.7467
• 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/R	None	None	0.002	N	0.149	0.081	0.0920862733494	gnomAD-4.0.0	3.18256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71687E-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
K/A	0.5722	likely_pathogenic	0.4845	ambiguous	-0.175	Destabilizing	0.25	N	0.394	neutral	None	None	None	None	N
K/C	0.7688	likely_pathogenic	0.7399	pathogenic	-0.278	Destabilizing	0.992	D	0.337	neutral	None	None	None	None	N
K/D	0.6928	likely_pathogenic	0.6057	pathogenic	0.043	Stabilizing	0.447	N	0.395	neutral	None	None	None	None	N
K/E	0.4779	ambiguous	0.3619	ambiguous	0.097	Stabilizing	0.334	N	0.365	neutral	N	0.460787574	None	None	N
K/F	0.9181	likely_pathogenic	0.8846	pathogenic	-0.098	Destabilizing	0.92	D	0.372	neutral	None	None	None	None	N
K/G	0.5299	ambiguous	0.4541	ambiguous	-0.47	Destabilizing	0.4	N	0.388	neutral	None	None	None	None	N
K/H	0.2922	likely_benign	0.2727	benign	-0.793	Destabilizing	0.92	D	0.355	neutral	None	None	None	None	N
K/I	0.8097	likely_pathogenic	0.7374	pathogenic	0.548	Stabilizing	0.447	N	0.391	neutral	None	None	None	None	N
K/L	0.6552	likely_pathogenic	0.5988	pathogenic	0.548	Stabilizing	0.447	N	0.398	neutral	None	None	None	None	N
K/M	0.5797	likely_pathogenic	0.4964	ambiguous	0.386	Stabilizing	0.896	D	0.353	neutral	N	0.462328386	None	None	N
K/N	0.4872	ambiguous	0.4055	ambiguous	-0.06	Destabilizing	0.016	N	0.303	neutral	N	0.43531034	None	None	N
K/P	0.7836	likely_pathogenic	0.765	pathogenic	0.338	Stabilizing	0.972	D	0.381	neutral	None	None	None	None	N
K/Q	0.205	likely_benign	0.1717	benign	-0.196	Destabilizing	0.549	D	0.383	neutral	N	0.46990849	None	None	N
K/R	0.0858	likely_benign	0.0846	benign	-0.297	Destabilizing	0.002	N	0.149	neutral	N	0.438854864	None	None	N
K/S	0.5587	ambiguous	0.467	ambiguous	-0.627	Destabilizing	0.059	N	0.225	neutral	None	None	None	None	N
K/T	0.382	ambiguous	0.3024	benign	-0.393	Destabilizing	0.549	D	0.381	neutral	N	0.46496403	None	None	N
K/V	0.7379	likely_pathogenic	0.6699	pathogenic	0.338	Stabilizing	0.021	N	0.276	neutral	None	None	None	None	N
K/W	0.8593	likely_pathogenic	0.8271	pathogenic	-0.034	Destabilizing	0.992	D	0.457	neutral	None	None	None	None	N
K/Y	0.7353	likely_pathogenic	0.6829	pathogenic	0.277	Stabilizing	0.972	D	0.375	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.