TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22511	67756;67757;67758	chr2:178579666;178579665;178579664	chr2:179444393;179444392;179444391
N2AB	20870	62833;62834;62835	chr2:178579666;178579665;178579664	chr2:179444393;179444392;179444391
N2A	19943	60052;60053;60054	chr2:178579666;178579665;178579664	chr2:179444393;179444392;179444391
N2B	13446	40561;40562;40563	chr2:178579666;178579665;178579664	chr2:179444393;179444392;179444391
Novex-1	13571	40936;40937;40938	chr2:178579666;178579665;178579664	chr2:179444393;179444392;179444391
Novex-2	13638	41137;41138;41139	chr2:178579666;178579665;178579664	chr2:179444393;179444392;179444391
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: Fn3-51
• Domain position: 61
• Structural Position: 94
• Q(SASA): 0.6336
• 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	rs368046394	0.308	0.001	N	0.154	0.134	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/R	rs368046394	0.308	0.001	N	0.154	0.134	None	gnomAD-4.0.0	2.05314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69897E-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	0.2035	likely_benign	0.2147	benign	-0.001	Destabilizing	0.061	N	0.285	neutral	None	None	None	None	N
K/C	0.6197	likely_pathogenic	0.6173	pathogenic	-0.171	Destabilizing	0.983	D	0.399	neutral	None	None	None	None	N
K/D	0.3427	ambiguous	0.3555	ambiguous	0.201	Stabilizing	0.418	N	0.405	neutral	None	None	None	None	N
K/E	0.1066	likely_benign	0.1192	benign	0.194	Stabilizing	0.183	N	0.351	neutral	N	0.4574117	None	None	N
K/F	0.6847	likely_pathogenic	0.7205	pathogenic	-0.301	Destabilizing	0.94	D	0.412	neutral	None	None	None	None	N
K/G	0.238	likely_benign	0.2597	benign	-0.173	Destabilizing	None	N	0.247	neutral	None	None	None	None	N
K/H	0.2927	likely_benign	0.3015	benign	-0.47	Destabilizing	0.836	D	0.429	neutral	None	None	None	None	N
K/I	0.3105	likely_benign	0.3299	benign	0.365	Stabilizing	0.794	D	0.449	neutral	N	0.505533721	None	None	N
K/L	0.3023	likely_benign	0.3293	benign	0.365	Stabilizing	0.418	N	0.431	neutral	None	None	None	None	N
K/M	0.2062	likely_benign	0.2226	benign	0.248	Stabilizing	0.94	D	0.431	neutral	None	None	None	None	N
K/N	0.2844	likely_benign	0.3072	benign	0.342	Stabilizing	0.351	N	0.32	neutral	N	0.493564501	None	None	N
K/P	0.4602	ambiguous	0.4668	ambiguous	0.27	Stabilizing	0.593	D	0.471	neutral	None	None	None	None	N
K/Q	0.1203	likely_benign	0.1273	benign	0.137	Stabilizing	0.351	N	0.35	neutral	N	0.469764922	None	None	N
K/R	0.0755	likely_benign	0.078	benign	0.066	Stabilizing	0.001	N	0.154	neutral	N	0.492391066	None	None	N
K/S	0.2404	likely_benign	0.2559	benign	-0.177	Destabilizing	0.012	N	0.143	neutral	None	None	None	None	N
K/T	0.1157	likely_benign	0.1201	benign	-0.042	Destabilizing	0.101	N	0.4	neutral	N	0.449560221	None	None	N
K/V	0.2375	likely_benign	0.2471	benign	0.27	Stabilizing	0.593	D	0.455	neutral	None	None	None	None	N
K/W	0.6511	likely_pathogenic	0.6921	pathogenic	-0.309	Destabilizing	0.983	D	0.409	neutral	None	None	None	None	N
K/Y	0.5742	likely_pathogenic	0.6022	pathogenic	0.061	Stabilizing	0.94	D	0.417	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.