TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22350	67273;67274;67275	chr2:178580331;178580330;178580329	chr2:179445058;179445057;179445056
N2AB	20709	62350;62351;62352	chr2:178580331;178580330;178580329	chr2:179445058;179445057;179445056
N2A	19782	59569;59570;59571	chr2:178580331;178580330;178580329	chr2:179445058;179445057;179445056
N2B	13285	40078;40079;40080	chr2:178580331;178580330;178580329	chr2:179445058;179445057;179445056
Novex-1	13410	40453;40454;40455	chr2:178580331;178580330;178580329	chr2:179445058;179445057;179445056
Novex-2	13477	40654;40655;40656	chr2:178580331;178580330;178580329	chr2:179445058;179445057;179445056
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: Ig-126
• Domain position: 86
• Structural Position: 175
• Q(SASA): 0.5943
• 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/Q	rs1370592733	0.005	0.957	N	0.643	0.354	0.33340067248	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
K/Q	rs1370592733	0.005	0.957	N	0.643	0.354	0.33340067248	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/Q	rs1370592733	0.005	0.957	N	0.643	0.354	0.33340067248	gnomAD-4.0.0	3.72098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08772E-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	0.9459	likely_pathogenic	0.9627	pathogenic	-0.339	Destabilizing	0.895	D	0.608	neutral	None	None	None	None	N
K/C	0.9652	likely_pathogenic	0.9716	pathogenic	-0.576	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
K/D	0.9689	likely_pathogenic	0.9789	pathogenic	0.052	Stabilizing	0.895	D	0.653	neutral	None	None	None	None	N
K/E	0.8382	likely_pathogenic	0.9033	pathogenic	0.165	Stabilizing	0.039	N	0.385	neutral	D	0.529056447	None	None	N
K/F	0.9928	likely_pathogenic	0.9952	pathogenic	-0.025	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/G	0.9746	likely_pathogenic	0.9829	pathogenic	-0.685	Destabilizing	0.983	D	0.641	neutral	None	None	None	None	N
K/H	0.7008	likely_pathogenic	0.7268	pathogenic	-0.847	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
K/I	0.9272	likely_pathogenic	0.9503	pathogenic	0.545	Stabilizing	0.989	D	0.736	prob.delet.	D	0.530616672	None	None	N
K/L	0.9062	likely_pathogenic	0.9329	pathogenic	0.545	Stabilizing	0.983	D	0.641	neutral	None	None	None	None	N
K/M	0.8406	likely_pathogenic	0.8873	pathogenic	0.139	Stabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/N	0.9253	likely_pathogenic	0.9516	pathogenic	-0.426	Destabilizing	0.978	D	0.649	neutral	N	0.501229825	None	None	N
K/P	0.9977	likely_pathogenic	0.9979	pathogenic	0.281	Stabilizing	0.992	D	0.712	prob.delet.	None	None	None	None	N
K/Q	0.548	ambiguous	0.644	pathogenic	-0.416	Destabilizing	0.957	D	0.643	neutral	N	0.483072664	None	None	N
K/R	0.1258	likely_benign	0.1353	benign	-0.452	Destabilizing	0.928	D	0.535	neutral	N	0.490751562	None	None	N
K/S	0.9446	likely_pathogenic	0.9637	pathogenic	-1.012	Destabilizing	0.895	D	0.589	neutral	None	None	None	None	N
K/T	0.7818	likely_pathogenic	0.8277	pathogenic	-0.697	Destabilizing	0.978	D	0.681	prob.neutral	D	0.523783913	None	None	N
K/V	0.8985	likely_pathogenic	0.9209	pathogenic	0.281	Stabilizing	0.983	D	0.69	prob.neutral	None	None	None	None	N
K/W	0.9841	likely_pathogenic	0.9877	pathogenic	0.028	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
K/Y	0.965	likely_pathogenic	0.9741	pathogenic	0.327	Stabilizing	0.997	D	0.706	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.