TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7755	23488;23489;23490	chr2:178720499;178720498;178720497	chr2:179585226;179585225;179585224
N2AB	7438	22537;22538;22539	chr2:178720499;178720498;178720497	chr2:179585226;179585225;179585224
N2A	6511	19756;19757;19758	chr2:178720499;178720498;178720497	chr2:179585226;179585225;179585224
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-62
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.6422
• 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
F/S	None	None	0.002	N	0.247	0.302	0.441017621159	gnomAD-4.0.0	6.84277E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99549E-07	0	0
F/Y	None	None	0.51	N	0.358	0.112	0.423360453849	gnomAD-4.0.0	6.84277E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99549E-07	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
F/A	0.2382	likely_benign	0.259	benign	-2.141	Highly Destabilizing	0.098	N	0.341	neutral	None	None	None	None	N
F/C	0.2215	likely_benign	0.2553	benign	-1.077	Destabilizing	0.952	D	0.441	neutral	N	0.474029883	None	None	N
F/D	0.4463	ambiguous	0.4888	ambiguous	-0.894	Destabilizing	0.199	N	0.463	neutral	None	None	None	None	N
F/E	0.5801	likely_pathogenic	0.6205	pathogenic	-0.794	Destabilizing	0.13	N	0.443	neutral	None	None	None	None	N
F/G	0.3902	ambiguous	0.4141	ambiguous	-2.482	Highly Destabilizing	0.001	N	0.276	neutral	None	None	None	None	N
F/H	0.3127	likely_benign	0.357	ambiguous	-0.79	Destabilizing	0.72	D	0.441	neutral	None	None	None	None	N
F/I	0.1735	likely_benign	0.1869	benign	-1.107	Destabilizing	0.433	N	0.296	neutral	N	0.465063683	None	None	N
F/K	0.5553	ambiguous	0.607	pathogenic	-1.235	Destabilizing	0.171	N	0.441	neutral	None	None	None	None	N
F/L	0.6478	likely_pathogenic	0.6866	pathogenic	-1.107	Destabilizing	0.135	N	0.236	neutral	N	0.486169674	None	None	N
F/M	0.349	ambiguous	0.3655	ambiguous	-0.805	Destabilizing	0.503	D	0.387	neutral	None	None	None	None	N
F/N	0.2887	likely_benign	0.3204	benign	-1.312	Destabilizing	0.007	N	0.301	neutral	None	None	None	None	N
F/P	0.8327	likely_pathogenic	0.8749	pathogenic	-1.446	Destabilizing	0.71	D	0.494	neutral	None	None	None	None	N
F/Q	0.4619	ambiguous	0.5079	ambiguous	-1.337	Destabilizing	0.423	N	0.495	neutral	None	None	None	None	N
F/R	0.4241	ambiguous	0.4679	ambiguous	-0.663	Destabilizing	0.333	N	0.489	neutral	None	None	None	None	N
F/S	0.1398	likely_benign	0.1529	benign	-2.09	Highly Destabilizing	0.002	N	0.247	neutral	N	0.390333851	None	None	N
F/T	0.1874	likely_benign	0.207	benign	-1.889	Destabilizing	0.199	N	0.407	neutral	None	None	None	None	N
F/V	0.1603	likely_benign	0.1748	benign	-1.446	Destabilizing	0.101	N	0.373	neutral	N	0.460137866	None	None	N
F/W	0.3816	ambiguous	0.4169	ambiguous	-0.387	Destabilizing	0.982	D	0.429	neutral	None	None	None	None	N
F/Y	0.1009	likely_benign	0.1085	benign	-0.62	Destabilizing	0.51	D	0.358	neutral	N	0.462466095	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.