TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8868	26827;26828;26829	chr2:178714056;178714055;178714054	chr2:179578783;179578782;179578781
N2AB	8551	25876;25877;25878	chr2:178714056;178714055;178714054	chr2:179578783;179578782;179578781
N2A	7624	23095;23096;23097	chr2:178714056;178714055;178714054	chr2:179578783;179578782;179578781
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-74
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.6354
• 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/E	None	None	0.425	N	0.285	0.139	0.348101942276	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79905E-06	0	0
K/N	None	None	0.002	N	0.207	0.103	0.0954503805726	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	0
K/Q	rs776511625	0.34	0.642	N	0.33	0.15	0.239901079897	gnomAD-2.1.1	4.02E-05	None	None	None	None	N	None	0	2.03524E-04	None	0	0	None	0	None	0	2.67E-05	0
K/Q	rs776511625	0.34	0.642	N	0.33	0.15	0.239901079897	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	1.96438E-04	0	0	0	None	0	0	2.94E-05	0	0
K/Q	rs776511625	0.34	0.642	N	0.33	0.15	0.239901079897	gnomAD-4.0.0	2.41707E-05	None	None	None	None	N	None	0	2.3352E-04	None	0	0	None	0	0	1.94961E-05	0	3.20307E-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
K/A	0.2617	likely_benign	0.2742	benign	-0.092	Destabilizing	0.495	N	0.371	neutral	None	None	None	None	N
K/C	0.5431	ambiguous	0.5466	ambiguous	-0.391	Destabilizing	0.995	D	0.309	neutral	None	None	None	None	N
K/D	0.4226	ambiguous	0.4629	ambiguous	0.168	Stabilizing	0.543	D	0.341	neutral	None	None	None	None	N
K/E	0.111	likely_benign	0.1236	benign	0.213	Stabilizing	0.425	N	0.285	neutral	N	0.476280755	None	None	N
K/F	0.5459	ambiguous	0.572	pathogenic	-0.136	Destabilizing	0.944	D	0.347	neutral	None	None	None	None	N
K/G	0.3829	ambiguous	0.4196	ambiguous	-0.336	Destabilizing	0.543	D	0.342	neutral	None	None	None	None	N
K/H	0.2244	likely_benign	0.2343	benign	-0.524	Destabilizing	0.017	N	0.229	neutral	None	None	None	None	N
K/I	0.1854	likely_benign	0.1823	benign	0.487	Stabilizing	0.023	N	0.313	neutral	N	0.498909685	None	None	N
K/L	0.2277	likely_benign	0.2329	benign	0.487	Stabilizing	0.329	N	0.333	neutral	None	None	None	None	N
K/M	0.1408	likely_benign	0.1486	benign	0.112	Stabilizing	0.944	D	0.315	neutral	None	None	None	None	N
K/N	0.2335	likely_benign	0.2476	benign	-0.024	Destabilizing	0.002	N	0.207	neutral	N	0.477918337	None	None	N
K/P	0.8978	likely_pathogenic	0.9213	pathogenic	0.323	Stabilizing	0.981	D	0.345	neutral	None	None	None	None	N
K/Q	0.0959	likely_benign	0.1	benign	-0.109	Destabilizing	0.642	D	0.33	neutral	N	0.441629463	None	None	N
K/R	0.0737	likely_benign	0.0764	benign	-0.155	Destabilizing	0.642	D	0.299	neutral	N	0.42854831	None	None	N
K/S	0.2813	likely_benign	0.2924	benign	-0.542	Destabilizing	0.329	N	0.282	neutral	None	None	None	None	N
K/T	0.1342	likely_benign	0.1368	benign	-0.329	Destabilizing	0.642	D	0.327	neutral	N	0.462930242	None	None	N
K/V	0.1792	likely_benign	0.1822	benign	0.323	Stabilizing	0.031	N	0.249	neutral	None	None	None	None	N
K/W	0.5889	likely_pathogenic	0.6173	pathogenic	-0.142	Destabilizing	0.995	D	0.347	neutral	None	None	None	None	N
K/Y	0.4398	ambiguous	0.4706	ambiguous	0.193	Stabilizing	0.893	D	0.345	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.