TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28418	85477;85478;85479	chr2:178560880;178560879;178560878	chr2:179425607;179425606;179425605
N2AB	26777	80554;80555;80556	chr2:178560880;178560879;178560878	chr2:179425607;179425606;179425605
N2A	25850	77773;77774;77775	chr2:178560880;178560879;178560878	chr2:179425607;179425606;179425605
N2B	19353	58282;58283;58284	chr2:178560880;178560879;178560878	chr2:179425607;179425606;179425605
Novex-1	19478	58657;58658;58659	chr2:178560880;178560879;178560878	chr2:179425607;179425606;179425605
Novex-2	19545	58858;58859;58860	chr2:178560880;178560879;178560878	chr2:179425607;179425606;179425605
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-143
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.265
• 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/E	None	None	0.92	D	0.386	0.323	0.426318900417	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85811E-06	0	0
K/N	rs759051213	-0.884	0.959	D	0.371	0.297	0.215109475489	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/N	rs759051213	-0.884	0.959	D	0.371	0.297	0.215109475489	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
K/A	0.6719	likely_pathogenic	0.6723	pathogenic	-0.468	Destabilizing	0.863	D	0.371	neutral	None	None	None	None	N
K/C	0.8779	likely_pathogenic	0.8708	pathogenic	-0.661	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
K/D	0.8674	likely_pathogenic	0.8593	pathogenic	-0.465	Destabilizing	0.969	D	0.424	neutral	None	None	None	None	N
K/E	0.4135	ambiguous	0.3929	ambiguous	-0.396	Destabilizing	0.92	D	0.386	neutral	D	0.530864601	None	None	N
K/F	0.9329	likely_pathogenic	0.9192	pathogenic	-0.456	Destabilizing	0.997	D	0.58	neutral	None	None	None	None	N
K/G	0.7342	likely_pathogenic	0.7494	pathogenic	-0.787	Destabilizing	0.969	D	0.464	neutral	None	None	None	None	N
K/H	0.5044	ambiguous	0.4853	ambiguous	-1.231	Destabilizing	0.997	D	0.487	neutral	None	None	None	None	N
K/I	0.6916	likely_pathogenic	0.6516	pathogenic	0.334	Stabilizing	0.976	D	0.572	neutral	N	0.503382646	None	None	N
K/L	0.6575	likely_pathogenic	0.6362	pathogenic	0.334	Stabilizing	0.939	D	0.449	neutral	None	None	None	None	N
K/M	0.4642	ambiguous	0.4477	ambiguous	0.371	Stabilizing	0.999	D	0.485	neutral	None	None	None	None	N
K/N	0.7393	likely_pathogenic	0.73	pathogenic	-0.432	Destabilizing	0.959	D	0.371	neutral	D	0.531731393	None	None	N
K/P	0.8781	likely_pathogenic	0.8915	pathogenic	0.097	Stabilizing	0.997	D	0.452	neutral	None	None	None	None	N
K/Q	0.2721	likely_benign	0.2668	benign	-0.663	Destabilizing	0.92	D	0.431	neutral	N	0.484692052	None	None	N
K/R	0.0973	likely_benign	0.0948	benign	-0.489	Destabilizing	0.015	N	0.081	neutral	N	0.459023145	None	None	N
K/S	0.7189	likely_pathogenic	0.7195	pathogenic	-1.044	Destabilizing	0.884	D	0.334	neutral	None	None	None	None	N
K/T	0.3657	ambiguous	0.3544	ambiguous	-0.788	Destabilizing	0.134	N	0.275	neutral	D	0.522399833	None	None	N
K/V	0.6558	likely_pathogenic	0.635	pathogenic	0.097	Stabilizing	0.939	D	0.464	neutral	None	None	None	None	N
K/W	0.8673	likely_pathogenic	0.8507	pathogenic	-0.341	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
K/Y	0.8462	likely_pathogenic	0.8264	pathogenic	0.022	Stabilizing	0.997	D	0.552	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.