TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14626	44101;44102;44103	chr2:178631172;178631171;178631170	chr2:179495899;179495898;179495897
N2AB	12985	39178;39179;39180	chr2:178631172;178631171;178631170	chr2:179495899;179495898;179495897
N2A	12058	36397;36398;36399	chr2:178631172;178631171;178631170	chr2:179495899;179495898;179495897
N2B	5561	16906;16907;16908	chr2:178631172;178631171;178631170	chr2:179495899;179495898;179495897
Novex-1	5686	17281;17282;17283	chr2:178631172;178631171;178631170	chr2:179495899;179495898;179495897
Novex-2	5753	17482;17483;17484	chr2:178631172;178631171;178631170	chr2:179495899;179495898;179495897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-97
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.8339
• 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/R	rs2059753756	None	0.029	N	0.327	0.098	0.362758974969	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	0	0
K/T	None	None	None	N	0.131	0.135	0.273503213844	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.1378	likely_benign	0.1454	benign	0.024	Stabilizing	0.007	N	0.254	neutral	None	None	None	None	N
K/C	0.6491	likely_pathogenic	0.6341	pathogenic	-0.475	Destabilizing	0.356	N	0.307	neutral	None	None	None	None	N
K/D	0.3015	likely_benign	0.3055	benign	-0.32	Destabilizing	0.016	N	0.327	neutral	None	None	None	None	N
K/E	0.0711	likely_benign	0.0785	benign	-0.325	Destabilizing	None	N	0.165	neutral	N	0.485336317	None	None	N
K/F	0.4207	ambiguous	0.4194	ambiguous	-0.287	Destabilizing	None	N	0.165	neutral	None	None	None	None	N
K/G	0.2729	likely_benign	0.2708	benign	-0.117	Destabilizing	0.031	N	0.297	neutral	None	None	None	None	N
K/H	0.2415	likely_benign	0.2332	benign	-0.218	Destabilizing	0.356	N	0.313	neutral	None	None	None	None	N
K/I	0.1169	likely_benign	0.1242	benign	0.311	Stabilizing	None	N	0.219	neutral	None	None	None	None	N
K/L	0.1475	likely_benign	0.1525	benign	0.311	Stabilizing	0.007	N	0.28	neutral	None	None	None	None	N
K/M	0.106	likely_benign	0.1112	benign	-0.117	Destabilizing	0.171	N	0.315	neutral	D	0.576467751	None	None	N
K/N	0.1848	likely_benign	0.1761	benign	-0.058	Destabilizing	0.055	N	0.265	neutral	N	0.490683503	None	None	N
K/P	0.3044	likely_benign	0.3394	benign	0.239	Stabilizing	0.136	N	0.405	neutral	None	None	None	None	N
K/Q	0.095	likely_benign	0.0954	benign	-0.18	Destabilizing	0.029	N	0.322	neutral	N	0.501281244	None	None	N
K/R	0.0961	likely_benign	0.0921	benign	-0.147	Destabilizing	0.029	N	0.327	neutral	N	0.482925248	None	None	N
K/S	0.1774	likely_benign	0.1777	benign	-0.398	Destabilizing	0.001	N	0.159	neutral	None	None	None	None	N
K/T	0.0709	likely_benign	0.0758	benign	-0.283	Destabilizing	None	N	0.131	neutral	N	0.439270189	None	None	N
K/V	0.1282	likely_benign	0.1375	benign	0.239	Stabilizing	0.007	N	0.285	neutral	None	None	None	None	N
K/W	0.6835	likely_pathogenic	0.651	pathogenic	-0.401	Destabilizing	0.864	D	0.303	neutral	None	None	None	None	N
K/Y	0.3878	ambiguous	0.3763	ambiguous	-0.049	Destabilizing	0.038	N	0.434	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.