TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24951	75076;75077;75078	chr2:178571281;178571280;178571279	chr2:179436008;179436007;179436006
N2AB	23310	70153;70154;70155	chr2:178571281;178571280;178571279	chr2:179436008;179436007;179436006
N2A	22383	67372;67373;67374	chr2:178571281;178571280;178571279	chr2:179436008;179436007;179436006
N2B	15886	47881;47882;47883	chr2:178571281;178571280;178571279	chr2:179436008;179436007;179436006
Novex-1	16011	48256;48257;48258	chr2:178571281;178571280;178571279	chr2:179436008;179436007;179436006
Novex-2	16078	48457;48458;48459	chr2:178571281;178571280;178571279	chr2:179436008;179436007;179436006
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-69
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.8677
• Predicted PPI site: I

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	None	None	0.919	N	0.521	0.286	0.186928172975	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.6275	likely_pathogenic	0.6069	pathogenic	-0.143	Destabilizing	0.938	D	0.528	neutral	None	None	None	None	I
N/C	0.6238	likely_pathogenic	0.6209	pathogenic	0.145	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
N/D	0.4801	ambiguous	0.485	ambiguous	0.019	Stabilizing	0.958	D	0.547	neutral	N	0.463743027	None	None	I
N/E	0.8428	likely_pathogenic	0.8423	pathogenic	-0.048	Destabilizing	0.968	D	0.508	neutral	None	None	None	None	I
N/F	0.8688	likely_pathogenic	0.8767	pathogenic	-0.739	Destabilizing	0.995	D	0.66	neutral	None	None	None	None	I
N/G	0.4763	ambiguous	0.4554	ambiguous	-0.23	Destabilizing	0.968	D	0.525	neutral	None	None	None	None	I
N/H	0.2927	likely_benign	0.2977	benign	-0.243	Destabilizing	0.998	D	0.605	neutral	N	0.487034412	None	None	I
N/I	0.709	likely_pathogenic	0.7023	pathogenic	-0.014	Destabilizing	0.988	D	0.653	neutral	N	0.487287901	None	None	I
N/K	0.7372	likely_pathogenic	0.7723	pathogenic	0.112	Stabilizing	0.958	D	0.507	neutral	N	0.499050466	None	None	I
N/L	0.5839	likely_pathogenic	0.5831	pathogenic	-0.014	Destabilizing	0.982	D	0.579	neutral	None	None	None	None	I
N/M	0.6783	likely_pathogenic	0.6844	pathogenic	0.124	Stabilizing	1.0	D	0.61	neutral	None	None	None	None	I
N/P	0.8796	likely_pathogenic	0.8594	pathogenic	-0.035	Destabilizing	0.995	D	0.591	neutral	None	None	None	None	I
N/Q	0.7298	likely_pathogenic	0.7348	pathogenic	-0.325	Destabilizing	0.995	D	0.576	neutral	None	None	None	None	I
N/R	0.7729	likely_pathogenic	0.7931	pathogenic	0.197	Stabilizing	0.991	D	0.585	neutral	None	None	None	None	I
N/S	0.1654	likely_benign	0.1563	benign	-0.068	Destabilizing	0.919	D	0.521	neutral	N	0.475634889	None	None	I
N/T	0.351	ambiguous	0.337	benign	-0.024	Destabilizing	0.067	N	0.443	neutral	N	0.519521739	None	None	I
N/V	0.701	likely_pathogenic	0.6983	pathogenic	-0.035	Destabilizing	0.982	D	0.611	neutral	None	None	None	None	I
N/W	0.9473	likely_pathogenic	0.949	pathogenic	-0.855	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
N/Y	0.4343	ambiguous	0.4615	ambiguous	-0.537	Destabilizing	0.998	D	0.611	neutral	N	0.494035851	None	None	I

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.