TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8744	26455;26456;26457	chr2:178714544;178714543;178714542	chr2:179579271;179579270;179579269
N2AB	8427	25504;25505;25506	chr2:178714544;178714543;178714542	chr2:179579271;179579270;179579269
N2A	7500	22723;22724;22725	chr2:178714544;178714543;178714542	chr2:179579271;179579270;179579269
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-73
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.9105
• 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
D/G	rs189391840	-0.078	0.001	N	0.187	0.319	None	gnomAD-2.1.1	2.03E-05	None	None	None	None	I	None	0	0	None	0	2.80238E-04	None	0	None	0	0	0
D/G	rs189391840	-0.078	0.001	N	0.187	0.319	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	0	0	0	7.7101E-04	None	0	0	0	0	0
D/G	rs189391840	-0.078	0.001	N	0.187	0.319	None	1000 genomes	5.99042E-04	None	None	None	None	I	None	0	0	None	None	3E-03	0	None	None	None	0	None
D/G	rs189391840	-0.078	0.001	N	0.187	0.319	None	gnomAD-4.0.0	4.97728E-06	None	None	None	None	I	None	0	0	None	0	1.78827E-04	None	0	0	0	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
D/A	0.1825	likely_benign	0.2826	benign	-0.1	Destabilizing	0.227	N	0.327	neutral	N	0.479155648	None	None	I
D/C	0.6657	likely_pathogenic	0.8129	pathogenic	0.258	Stabilizing	0.978	D	0.41	neutral	None	None	None	None	I
D/E	0.2068	likely_benign	0.2997	benign	-0.195	Destabilizing	0.062	N	0.308	neutral	N	0.51044839	None	None	I
D/F	0.6596	likely_pathogenic	0.8285	pathogenic	-0.2	Destabilizing	0.993	D	0.409	neutral	None	None	None	None	I
D/G	0.1536	likely_benign	0.2324	benign	-0.249	Destabilizing	0.001	N	0.187	neutral	N	0.489751485	None	None	I
D/H	0.2811	likely_benign	0.4212	ambiguous	0.019	Stabilizing	0.931	D	0.337	neutral	N	0.509376677	None	None	I
D/I	0.4566	ambiguous	0.6753	pathogenic	0.228	Stabilizing	0.98	D	0.405	neutral	None	None	None	None	I
D/K	0.4635	ambiguous	0.6533	pathogenic	0.647	Stabilizing	0.871	D	0.32	neutral	None	None	None	None	I
D/L	0.4937	ambiguous	0.6925	pathogenic	0.228	Stabilizing	0.98	D	0.404	neutral	None	None	None	None	I
D/M	0.6574	likely_pathogenic	0.829	pathogenic	0.334	Stabilizing	0.995	D	0.391	neutral	None	None	None	None	I
D/N	0.0799	likely_benign	0.0964	benign	0.384	Stabilizing	0.001	N	0.139	neutral	N	0.456805907	None	None	I
D/P	0.554	ambiguous	0.6889	pathogenic	0.14	Stabilizing	0.743	D	0.339	neutral	None	None	None	None	I
D/Q	0.4091	ambiguous	0.578	pathogenic	0.394	Stabilizing	0.947	D	0.301	neutral	None	None	None	None	I
D/R	0.4813	ambiguous	0.6778	pathogenic	0.687	Stabilizing	0.96	D	0.386	neutral	None	None	None	None	I
D/S	0.107	likely_benign	0.1466	benign	0.314	Stabilizing	0.068	N	0.193	neutral	None	None	None	None	I
D/T	0.2333	likely_benign	0.3482	ambiguous	0.434	Stabilizing	0.457	N	0.315	neutral	None	None	None	None	I
D/V	0.2988	likely_benign	0.4776	ambiguous	0.14	Stabilizing	0.864	D	0.404	neutral	N	0.482118162	None	None	I
D/W	0.9123	likely_pathogenic	0.9612	pathogenic	-0.13	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	I
D/Y	0.2839	likely_benign	0.4362	ambiguous	0.036	Stabilizing	0.991	D	0.409	neutral	N	0.491272422	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.