TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17485	52678;52679;52680	chr2:178608430;178608429;178608428	chr2:179473157;179473156;179473155
N2AB	15844	47755;47756;47757	chr2:178608430;178608429;178608428	chr2:179473157;179473156;179473155
N2A	14917	44974;44975;44976	chr2:178608430;178608429;178608428	chr2:179473157;179473156;179473155
N2B	8420	25483;25484;25485	chr2:178608430;178608429;178608428	chr2:179473157;179473156;179473155
Novex-1	8545	25858;25859;25860	chr2:178608430;178608429;178608428	chr2:179473157;179473156;179473155
Novex-2	8612	26059;26060;26061	chr2:178608430;178608429;178608428	chr2:179473157;179473156;179473155
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-15
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.6373
• 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
N/S	rs965152631	None	0.31	N	0.161	0.09	0.110078149338	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.2703	likely_benign	0.2528	benign	-0.543	Destabilizing	0.759	D	0.394	neutral	None	None	None	None	N
N/C	0.3302	likely_benign	0.2782	benign	0.297	Stabilizing	0.999	D	0.429	neutral	None	None	None	None	N
N/D	0.1418	likely_benign	0.1492	benign	-0.563	Destabilizing	0.92	D	0.443	neutral	N	0.403945362	None	None	N
N/E	0.3858	ambiguous	0.3888	ambiguous	-0.599	Destabilizing	0.939	D	0.384	neutral	None	None	None	None	N
N/F	0.6273	likely_pathogenic	0.571	pathogenic	-1.027	Destabilizing	0.991	D	0.427	neutral	None	None	None	None	N
N/G	0.3208	likely_benign	0.2885	benign	-0.697	Destabilizing	0.939	D	0.373	neutral	None	None	None	None	N
N/H	0.116	likely_benign	0.1093	benign	-0.868	Destabilizing	0.077	N	0.312	neutral	N	0.455683691	None	None	N
N/I	0.4455	ambiguous	0.4211	ambiguous	-0.215	Destabilizing	0.976	D	0.437	neutral	N	0.475803011	None	None	N
N/K	0.2948	likely_benign	0.3101	benign	0.123	Stabilizing	0.92	D	0.393	neutral	N	0.491527061	None	None	N
N/L	0.3544	ambiguous	0.3236	benign	-0.215	Destabilizing	0.939	D	0.431	neutral	None	None	None	None	N
N/M	0.4384	ambiguous	0.4009	ambiguous	0.524	Stabilizing	0.999	D	0.403	neutral	None	None	None	None	N
N/P	0.9424	likely_pathogenic	0.9381	pathogenic	-0.301	Destabilizing	0.991	D	0.419	neutral	None	None	None	None	N
N/Q	0.3182	likely_benign	0.314	benign	-0.587	Destabilizing	0.991	D	0.401	neutral	None	None	None	None	N
N/R	0.3184	likely_benign	0.3209	benign	0.297	Stabilizing	0.991	D	0.369	neutral	None	None	None	None	N
N/S	0.0765	likely_benign	0.0748	benign	-0.183	Destabilizing	0.31	N	0.161	neutral	N	0.408561748	None	None	N
N/T	0.1248	likely_benign	0.1174	benign	-0.088	Destabilizing	0.061	N	0.092	neutral	N	0.438841795	None	None	N
N/V	0.378	ambiguous	0.3467	ambiguous	-0.301	Destabilizing	0.939	D	0.411	neutral	None	None	None	None	N
N/W	0.8412	likely_pathogenic	0.8198	pathogenic	-0.947	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
N/Y	0.236	likely_benign	0.2175	benign	-0.663	Destabilizing	0.976	D	0.43	neutral	N	0.516020074	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.