TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25475	76648;76649;76650	chr2:178569709;178569708;178569707	chr2:179434436;179434435;179434434
N2AB	23834	71725;71726;71727	chr2:178569709;178569708;178569707	chr2:179434436;179434435;179434434
N2A	22907	68944;68945;68946	chr2:178569709;178569708;178569707	chr2:179434436;179434435;179434434
N2B	16410	49453;49454;49455	chr2:178569709;178569708;178569707	chr2:179434436;179434435;179434434
Novex-1	16535	49828;49829;49830	chr2:178569709;178569708;178569707	chr2:179434436;179434435;179434434
Novex-2	16602	50029;50030;50031	chr2:178569709;178569708;178569707	chr2:179434436;179434435;179434434
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-73
• Domain position: 71
• Structural Position: 102
• Q(SASA): 0.2398
• 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
H/L	rs375737413	None	0.007	N	0.258	0.24	None	gnomAD-4.0.0	1.59292E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	0	None	0	0	0	0	0
H/Q	rs1707436468	None	0.028	N	0.224	0.142	0.156986980423	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
H/Q	rs1707436468	None	0.028	N	0.224	0.142	0.156986980423	gnomAD-4.0.0	6.84512E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99637E-07	0	0
H/R	rs375737413	None	0.521	N	0.336	0.18	0.1749357433	gnomAD-4.0.0	1.59292E-06	None	None	None	None	N	None	0	2.28906E-05	None	0	0	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
H/A	0.2846	likely_benign	0.2656	benign	-0.964	Destabilizing	0.543	D	0.345	neutral	None	None	None	None	N
H/C	0.1445	likely_benign	0.1437	benign	0.084	Stabilizing	0.996	D	0.459	neutral	None	None	None	None	N
H/D	0.2716	likely_benign	0.2572	benign	-0.892	Destabilizing	0.684	D	0.41	neutral	N	0.466315902	None	None	N
H/E	0.2381	likely_benign	0.2298	benign	-0.757	Destabilizing	0.373	N	0.325	neutral	None	None	None	None	N
H/F	0.3852	ambiguous	0.3804	ambiguous	0.614	Stabilizing	0.91	D	0.391	neutral	None	None	None	None	N
H/G	0.2787	likely_benign	0.2515	benign	-1.358	Destabilizing	0.742	D	0.377	neutral	None	None	None	None	N
H/I	0.3846	ambiguous	0.3645	ambiguous	0.157	Stabilizing	0.835	D	0.483	neutral	None	None	None	None	N
H/K	0.1581	likely_benign	0.153	benign	-0.498	Destabilizing	0.037	N	0.211	neutral	None	None	None	None	N
H/L	0.1886	likely_benign	0.1711	benign	0.157	Stabilizing	0.007	N	0.258	neutral	N	0.478768407	None	None	N
H/M	0.4108	ambiguous	0.4036	ambiguous	0.03	Stabilizing	0.91	D	0.425	neutral	None	None	None	None	N
H/N	0.1081	likely_benign	0.1057	benign	-0.831	Destabilizing	0.684	D	0.374	neutral	N	0.444117116	None	None	N
H/P	0.6676	likely_pathogenic	0.6071	pathogenic	-0.2	Destabilizing	0.939	D	0.441	neutral	N	0.478179186	None	None	N
H/Q	0.1175	likely_benign	0.1142	benign	-0.556	Destabilizing	0.028	N	0.224	neutral	N	0.407502955	None	None	N
H/R	0.083	likely_benign	0.0766	benign	-0.997	Destabilizing	0.521	D	0.336	neutral	N	0.448405428	None	None	N
H/S	0.2315	likely_benign	0.2214	benign	-0.799	Destabilizing	0.742	D	0.347	neutral	None	None	None	None	N
H/T	0.2199	likely_benign	0.2147	benign	-0.555	Destabilizing	0.742	D	0.429	neutral	None	None	None	None	N
H/V	0.2832	likely_benign	0.2752	benign	-0.2	Destabilizing	0.59	D	0.453	neutral	None	None	None	None	N
H/W	0.4853	ambiguous	0.4559	ambiguous	1.027	Stabilizing	0.996	D	0.451	neutral	None	None	None	None	N
H/Y	0.1322	likely_benign	0.1306	benign	0.958	Stabilizing	0.931	D	0.431	neutral	N	0.478432676	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.