TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15420	46483;46484;46485	chr2:178620263;178620262;178620261	chr2:179484990;179484989;179484988
N2AB	13779	41560;41561;41562	chr2:178620263;178620262;178620261	chr2:179484990;179484989;179484988
N2A	12852	38779;38780;38781	chr2:178620263;178620262;178620261	chr2:179484990;179484989;179484988
N2B	6355	19288;19289;19290	chr2:178620263;178620262;178620261	chr2:179484990;179484989;179484988
Novex-1	6480	19663;19664;19665	chr2:178620263;178620262;178620261	chr2:179484990;179484989;179484988
Novex-2	6547	19864;19865;19866	chr2:178620263;178620262;178620261	chr2:179484990;179484989;179484988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-106
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.8883
• 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
N/D	rs2058069795	None	None	N	0.087	0.111	0.202086224978	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
N/D	rs2058069795	None	None	N	0.087	0.111	0.202086224978	gnomAD-4.0.0	2.82719E-06	None	None	None	None	N	None	0	4.24737E-05	None	0	0	None	0	0	0	0	0
N/S	None	None	0.003	N	0.139	0.094	0.143124449307	gnomAD-4.0.0	2.15934E-06	None	None	None	None	N	None	0	0	None	0	2.56397E-05	None	0	0	1.85211E-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
N/A	0.14	likely_benign	0.1626	benign	-0.114	Destabilizing	0.001	N	0.199	neutral	None	None	None	None	N
N/C	0.336	likely_benign	0.3934	ambiguous	0.353	Stabilizing	0.942	D	0.311	neutral	None	None	None	None	N
N/D	0.1339	likely_benign	0.1401	benign	0.117	Stabilizing	None	N	0.087	neutral	N	0.403669189	None	None	N
N/E	0.2728	likely_benign	0.3202	benign	0.075	Stabilizing	0.004	N	0.128	neutral	None	None	None	None	N
N/F	0.4329	ambiguous	0.5082	ambiguous	-0.577	Destabilizing	0.428	N	0.441	neutral	None	None	None	None	N
N/G	0.2312	likely_benign	0.272	benign	-0.256	Destabilizing	0.063	N	0.179	neutral	None	None	None	None	N
N/H	0.1299	likely_benign	0.1275	benign	-0.324	Destabilizing	0.924	D	0.303	neutral	N	0.469703158	None	None	N
N/I	0.1488	likely_benign	0.179	benign	0.171	Stabilizing	0.002	N	0.307	neutral	N	0.496047201	None	None	N
N/K	0.2487	likely_benign	0.2711	benign	0.1	Stabilizing	0.189	N	0.216	neutral	N	0.424672255	None	None	N
N/L	0.1744	likely_benign	0.2034	benign	0.171	Stabilizing	0.001	N	0.28	neutral	None	None	None	None	N
N/M	0.2471	likely_benign	0.2896	benign	0.244	Stabilizing	0.724	D	0.328	neutral	None	None	None	None	N
N/P	0.288	likely_benign	0.3433	ambiguous	0.101	Stabilizing	0.603	D	0.4	neutral	None	None	None	None	N
N/Q	0.2563	likely_benign	0.2873	benign	-0.13	Destabilizing	0.428	N	0.245	neutral	None	None	None	None	N
N/R	0.2911	likely_benign	0.3072	benign	0.124	Stabilizing	0.428	N	0.247	neutral	None	None	None	None	N
N/S	0.0801	likely_benign	0.0794	benign	0.069	Stabilizing	0.003	N	0.139	neutral	N	0.450847904	None	None	N
N/T	0.0944	likely_benign	0.1042	benign	0.147	Stabilizing	0.104	N	0.199	neutral	N	0.443179505	None	None	N
N/V	0.1522	likely_benign	0.1749	benign	0.101	Stabilizing	0.023	N	0.265	neutral	None	None	None	None	N
N/W	0.7191	likely_pathogenic	0.7734	pathogenic	-0.675	Destabilizing	0.984	D	0.325	neutral	None	None	None	None	N
N/Y	0.1972	likely_benign	0.2146	benign	-0.37	Destabilizing	0.801	D	0.409	neutral	N	0.504725402	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.