TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22882	68869;68870;68871	chr2:178577782;178577781;178577780	chr2:179442509;179442508;179442507
N2AB	21241	63946;63947;63948	chr2:178577782;178577781;178577780	chr2:179442509;179442508;179442507
N2A	20314	61165;61166;61167	chr2:178577782;178577781;178577780	chr2:179442509;179442508;179442507
N2B	13817	41674;41675;41676	chr2:178577782;178577781;178577780	chr2:179442509;179442508;179442507
Novex-1	13942	42049;42050;42051	chr2:178577782;178577781;178577780	chr2:179442509;179442508;179442507
Novex-2	14009	42250;42251;42252	chr2:178577782;178577781;178577780	chr2:179442509;179442508;179442507
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-54
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.1963
• 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
D/E	None	None	0.001	N	0.195	0.039	0.168933306366	gnomAD-4.0.0	1.59244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02535E-05

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
D/A	0.1791	likely_benign	0.1865	benign	-0.48	Destabilizing	0.201	N	0.53	neutral	N	0.465341624	None	None	N
D/C	0.573	likely_pathogenic	0.5891	pathogenic	-0.219	Destabilizing	0.982	D	0.685	prob.neutral	None	None	None	None	N
D/E	0.1234	likely_benign	0.1251	benign	-0.793	Destabilizing	0.001	N	0.195	neutral	N	0.392186786	None	None	N
D/F	0.5499	ambiguous	0.5632	ambiguous	-0.034	Destabilizing	0.935	D	0.701	prob.neutral	None	None	None	None	N
D/G	0.2647	likely_benign	0.2662	benign	-0.867	Destabilizing	0.334	N	0.51	neutral	N	0.521828538	None	None	N
D/H	0.3325	likely_benign	0.3411	ambiguous	-0.432	Destabilizing	0.931	D	0.608	neutral	N	0.49054945	None	None	N
D/I	0.2758	likely_benign	0.2862	benign	0.553	Stabilizing	0.826	D	0.72	prob.delet.	None	None	None	None	N
D/K	0.4281	ambiguous	0.4555	ambiguous	-0.432	Destabilizing	0.25	N	0.475	neutral	None	None	None	None	N
D/L	0.2938	likely_benign	0.3085	benign	0.553	Stabilizing	0.7	D	0.696	prob.neutral	None	None	None	None	N
D/M	0.4966	ambiguous	0.5148	ambiguous	1.02	Stabilizing	0.982	D	0.671	neutral	None	None	None	None	N
D/N	0.1264	likely_benign	0.1279	benign	-0.917	Destabilizing	0.334	N	0.509	neutral	N	0.490966913	None	None	N
D/P	0.5567	ambiguous	0.5623	ambiguous	0.235	Stabilizing	0.826	D	0.601	neutral	None	None	None	None	N
D/Q	0.3231	likely_benign	0.3322	benign	-0.743	Destabilizing	0.539	D	0.521	neutral	None	None	None	None	N
D/R	0.4988	ambiguous	0.5195	ambiguous	-0.298	Destabilizing	0.539	D	0.636	neutral	None	None	None	None	N
D/S	0.1517	likely_benign	0.1544	benign	-1.209	Destabilizing	0.25	N	0.457	neutral	None	None	None	None	N
D/T	0.2682	likely_benign	0.2782	benign	-0.884	Destabilizing	0.7	D	0.525	neutral	None	None	None	None	N
D/V	0.1769	likely_benign	0.1842	benign	0.235	Stabilizing	0.638	D	0.689	prob.neutral	N	0.518596232	None	None	N
D/W	0.8685	likely_pathogenic	0.8786	pathogenic	0.118	Stabilizing	0.982	D	0.665	neutral	None	None	None	None	N
D/Y	0.2337	likely_benign	0.2442	benign	0.21	Stabilizing	0.916	D	0.703	prob.neutral	N	0.509667663	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.