TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23051	69376;69377;69378	chr2:178577184;178577183;178577182	chr2:179441911;179441910;179441909
N2AB	21410	64453;64454;64455	chr2:178577184;178577183;178577182	chr2:179441911;179441910;179441909
N2A	20483	61672;61673;61674	chr2:178577184;178577183;178577182	chr2:179441911;179441910;179441909
N2B	13986	42181;42182;42183	chr2:178577184;178577183;178577182	chr2:179441911;179441910;179441909
Novex-1	14111	42556;42557;42558	chr2:178577184;178577183;178577182	chr2:179441911;179441910;179441909
Novex-2	14178	42757;42758;42759	chr2:178577184;178577183;178577182	chr2:179441911;179441910;179441909
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: Fn3-55
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6511
• 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/H	None	None	0.97	N	0.565	0.286	0.19670166235	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	0	0	None	0	2.78676E-05	None	0	0	0	0	0
N/T	None	None	0.698	N	0.549	0.122	0.265010934533	gnomAD-4.0.0	3.1856E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41779E-04	2.86061E-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	0.1681	likely_benign	0.169	benign	-0.245	Destabilizing	0.754	D	0.555	neutral	None	None	None	None	N
N/C	0.2622	likely_benign	0.2431	benign	0.349	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	N
N/D	0.1608	likely_benign	0.1665	benign	0.157	Stabilizing	0.698	D	0.601	neutral	N	0.430457172	None	None	N
N/E	0.4338	ambiguous	0.453	ambiguous	0.101	Stabilizing	0.019	N	0.234	neutral	None	None	None	None	N
N/F	0.5143	ambiguous	0.5042	ambiguous	-0.758	Destabilizing	0.993	D	0.66	neutral	None	None	None	None	N
N/G	0.1775	likely_benign	0.1829	benign	-0.371	Destabilizing	0.559	D	0.572	neutral	None	None	None	None	N
N/H	0.1018	likely_benign	0.0992	benign	-0.446	Destabilizing	0.97	D	0.565	neutral	N	0.502109414	None	None	N
N/I	0.3518	ambiguous	0.3517	ambiguous	-0.01	Destabilizing	0.97	D	0.646	neutral	N	0.469473135	None	None	N
N/K	0.4492	ambiguous	0.4497	ambiguous	0.227	Stabilizing	0.698	D	0.547	neutral	N	0.466129971	None	None	N
N/L	0.2588	likely_benign	0.2648	benign	-0.01	Destabilizing	0.956	D	0.534	neutral	None	None	None	None	N
N/M	0.3401	ambiguous	0.3442	ambiguous	0.322	Stabilizing	0.998	D	0.619	neutral	None	None	None	None	N
N/P	0.7738	likely_pathogenic	0.8054	pathogenic	-0.064	Destabilizing	0.978	D	0.607	neutral	None	None	None	None	N
N/Q	0.3364	likely_benign	0.342	ambiguous	-0.243	Destabilizing	0.915	D	0.522	neutral	None	None	None	None	N
N/R	0.4358	ambiguous	0.4268	ambiguous	0.279	Stabilizing	0.956	D	0.523	neutral	None	None	None	None	N
N/S	0.0678	likely_benign	0.0673	benign	0.011	Stabilizing	0.058	N	0.109	neutral	N	0.433497478	None	None	N
N/T	0.135	likely_benign	0.1407	benign	0.085	Stabilizing	0.698	D	0.549	neutral	N	0.49935711	None	None	N
N/V	0.2771	likely_benign	0.2797	benign	-0.064	Destabilizing	0.956	D	0.576	neutral	None	None	None	None	N
N/W	0.7654	likely_pathogenic	0.7488	pathogenic	-0.797	Destabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
N/Y	0.1906	likely_benign	0.1881	benign	-0.499	Destabilizing	0.99	D	0.632	neutral	D	0.522850045	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.