TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3360	10303;10304;10305	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938
N2AB	3360	10303;10304;10305	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938
N2A	3360	10303;10304;10305	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938
N2B	3314	10165;10166;10167	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938
Novex-1	3314	10165;10166;10167	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938
Novex-2	3314	10165;10166;10167	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938
Novex-3	3360	10303;10304;10305	chr2:178764213;178764212;178764211	chr2:179628940;179628939;179628938

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-24
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3811
• 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
Q/H	None	None	None	N	0.24	0.112	0.151104730317	gnomAD-4.0.0	6.84092E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99324E-07	0	0
Q/K	rs1259534996	None	0.012	N	0.245	0.123	0.199424873507	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
Q/K	rs1259534996	None	0.012	N	0.245	0.123	0.199424873507	gnomAD-4.0.0	1.31427E-05	None	None	None	None	N	None	4.82625E-05	0	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
Q/A	0.2427	likely_benign	0.2319	benign	-0.34	Destabilizing	0.031	N	0.328	neutral	None	None	None	None	N
Q/C	0.448	ambiguous	0.2829	benign	0.278	Stabilizing	0.864	D	0.373	neutral	None	None	None	None	N
Q/D	0.4762	ambiguous	0.4123	ambiguous	-0.181	Destabilizing	0.016	N	0.207	neutral	None	None	None	None	N
Q/E	0.1079	likely_benign	0.1123	benign	-0.205	Destabilizing	None	N	0.129	neutral	N	0.45741408	None	None	N
Q/F	0.5103	ambiguous	0.4395	ambiguous	-0.499	Destabilizing	0.356	N	0.401	neutral	None	None	None	None	N
Q/G	0.2546	likely_benign	0.2023	benign	-0.553	Destabilizing	0.072	N	0.359	neutral	None	None	None	None	N
Q/H	0.1764	likely_benign	0.137	benign	-0.563	Destabilizing	None	N	0.24	neutral	N	0.512666787	None	None	N
Q/I	0.3226	likely_benign	0.3064	benign	0.138	Stabilizing	0.356	N	0.435	neutral	None	None	None	None	N
Q/K	0.0797	likely_benign	0.0793	benign	0.025	Stabilizing	0.012	N	0.245	neutral	N	0.501628429	None	None	N
Q/L	0.115	likely_benign	0.108	benign	0.138	Stabilizing	0.055	N	0.359	neutral	D	0.595097553	None	None	N
Q/M	0.3098	likely_benign	0.2767	benign	0.619	Stabilizing	0.628	D	0.288	neutral	None	None	None	None	N
Q/N	0.2855	likely_benign	0.2594	benign	-0.274	Destabilizing	0.072	N	0.184	neutral	None	None	None	None	N
Q/P	0.636	likely_pathogenic	0.624	pathogenic	0.007	Stabilizing	0.106	N	0.379	neutral	D	0.63476693	None	None	N
Q/R	0.0736	likely_benign	0.0649	benign	0.188	Stabilizing	None	N	0.131	neutral	N	0.510554556	None	None	N
Q/S	0.2405	likely_benign	0.2289	benign	-0.297	Destabilizing	0.031	N	0.209	neutral	None	None	None	None	N
Q/T	0.2266	likely_benign	0.2102	benign	-0.162	Destabilizing	0.072	N	0.328	neutral	None	None	None	None	N
Q/V	0.2451	likely_benign	0.2387	benign	0.007	Stabilizing	0.072	N	0.409	neutral	None	None	None	None	N
Q/W	0.3545	ambiguous	0.2529	benign	-0.431	Destabilizing	0.864	D	0.379	neutral	None	None	None	None	N
Q/Y	0.3419	ambiguous	0.283	benign	-0.19	Destabilizing	0.214	N	0.381	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.