TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22934	69025;69026;69027	chr2:178577626;178577625;178577624	chr2:179442353;179442352;179442351
N2AB	21293	64102;64103;64104	chr2:178577626;178577625;178577624	chr2:179442353;179442352;179442351
N2A	20366	61321;61322;61323	chr2:178577626;178577625;178577624	chr2:179442353;179442352;179442351
N2B	13869	41830;41831;41832	chr2:178577626;178577625;178577624	chr2:179442353;179442352;179442351
Novex-1	13994	42205;42206;42207	chr2:178577626;178577625;178577624	chr2:179442353;179442352;179442351
Novex-2	14061	42406;42407;42408	chr2:178577626;178577625;178577624	chr2:179442353;179442352;179442351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-54
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.2544
• 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
T/A	rs749399592	-0.755	0.001	N	0.153	0.108	None	gnomAD-2.1.1	8.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
T/A	rs749399592	-0.755	0.001	N	0.153	0.108	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs749399592	-0.755	0.001	N	0.153	0.108	None	gnomAD-4.0.0	3.59995E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.92071E-05	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
T/A	0.0658	likely_benign	0.0664	benign	-0.462	Destabilizing	0.001	N	0.153	neutral	N	0.408455465	None	None	N
T/C	0.342	ambiguous	0.3618	ambiguous	-0.408	Destabilizing	0.967	D	0.569	neutral	None	None	None	None	N
T/D	0.2941	likely_benign	0.3004	benign	0.324	Stabilizing	0.691	D	0.643	neutral	None	None	None	None	N
T/E	0.2235	likely_benign	0.2302	benign	0.299	Stabilizing	0.524	D	0.633	neutral	None	None	None	None	N
T/F	0.2514	likely_benign	0.2558	benign	-0.66	Destabilizing	0.003	N	0.467	neutral	None	None	None	None	N
T/G	0.2174	likely_benign	0.2135	benign	-0.672	Destabilizing	0.355	N	0.601	neutral	None	None	None	None	N
T/H	0.2688	likely_benign	0.2658	benign	-0.83	Destabilizing	0.989	D	0.615	neutral	None	None	None	None	N
T/I	0.144	likely_benign	0.1392	benign	-0.015	Destabilizing	0.294	N	0.616	neutral	N	0.51606572	None	None	N
T/K	0.2225	likely_benign	0.2186	benign	-0.451	Destabilizing	0.524	D	0.626	neutral	None	None	None	None	N
T/L	0.0998	likely_benign	0.0991	benign	-0.015	Destabilizing	0.001	N	0.256	neutral	None	None	None	None	N
T/M	0.0835	likely_benign	0.0817	benign	-0.015	Destabilizing	0.794	D	0.595	neutral	None	None	None	None	N
T/N	0.0954	likely_benign	0.0963	benign	-0.342	Destabilizing	0.855	D	0.545	neutral	N	0.50869703	None	None	N
T/P	0.0755	likely_benign	0.0733	benign	-0.132	Destabilizing	0.003	N	0.376	neutral	N	0.379634068	None	None	N
T/Q	0.2141	likely_benign	0.2115	benign	-0.476	Destabilizing	0.887	D	0.614	neutral	None	None	None	None	N
T/R	0.1991	likely_benign	0.1945	benign	-0.208	Destabilizing	0.887	D	0.649	prob.neutral	None	None	None	None	N
T/S	0.1051	likely_benign	0.1049	benign	-0.631	Destabilizing	0.146	N	0.468	neutral	N	0.467599769	None	None	N
T/V	0.1166	likely_benign	0.1141	benign	-0.132	Destabilizing	0.185	N	0.42	neutral	None	None	None	None	N
T/W	0.5944	likely_pathogenic	0.6012	pathogenic	-0.641	Destabilizing	0.989	D	0.639	neutral	None	None	None	None	N
T/Y	0.2436	likely_benign	0.2614	benign	-0.377	Destabilizing	0.659	D	0.653	prob.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.