TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4704	14335;14336;14337	chr2:178738343;178738342;178738341	chr2:179603070;179603069;179603068
N2AB	4387	13384;13385;13386	chr2:178738343;178738342;178738341	chr2:179603070;179603069;179603068
N2A	3460	10603;10604;10605	chr2:178738343;178738342;178738341	chr2:179603070;179603069;179603068
N2B	4341	13246;13247;13248	chr2:178738343;178738342;178738341	chr2:179603070;179603069;179603068
Novex-1	4466	13621;13622;13623	chr2:178738343;178738342;178738341	chr2:179603070;179603069;179603068
Novex-2	4533	13822;13823;13824	chr2:178738343;178738342;178738341	chr2:179603070;179603069;179603068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-30
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.8242
• 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
R/G	rs775443847	-0.111	0.055	N	0.425	0.24	0.420447328233	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
R/G	rs775443847	-0.111	0.055	N	0.425	0.24	0.420447328233	gnomAD-4.0.0	1.59525E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43538E-05	0
R/K	None	None	None	N	0.127	0.123	0.236278675362	gnomAD-4.0.0	1.59526E-06	None	None	None	None	N	None	5.66316E-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
R/A	0.3916	ambiguous	0.452	ambiguous	-0.578	Destabilizing	0.016	N	0.339	neutral	None	None	None	None	N
R/C	0.2492	likely_benign	0.2981	benign	-0.489	Destabilizing	0.864	D	0.319	neutral	None	None	None	None	N
R/D	0.6469	likely_pathogenic	0.6987	pathogenic	0.017	Stabilizing	0.072	N	0.449	neutral	None	None	None	None	N
R/E	0.2779	likely_benign	0.3396	benign	0.148	Stabilizing	0.016	N	0.275	neutral	None	None	None	None	N
R/F	0.6116	likely_pathogenic	0.6854	pathogenic	-0.342	Destabilizing	0.214	N	0.367	neutral	None	None	None	None	N
R/G	0.2213	likely_benign	0.2734	benign	-0.902	Destabilizing	0.055	N	0.425	neutral	N	0.51177777	None	None	N
R/H	0.1156	likely_benign	0.124	benign	-1.285	Destabilizing	0.356	N	0.285	neutral	None	None	None	None	N
R/I	0.3086	likely_benign	0.3678	ambiguous	0.29	Stabilizing	0.038	N	0.434	neutral	None	None	None	None	N
R/K	0.0765	likely_benign	0.0785	benign	-0.631	Destabilizing	None	N	0.127	neutral	N	0.413419261	None	None	N
R/L	0.2868	likely_benign	0.3359	benign	0.29	Stabilizing	None	N	0.203	neutral	None	None	None	None	N
R/M	0.2509	likely_benign	0.2889	benign	-0.113	Destabilizing	0.171	N	0.329	neutral	N	0.515083035	None	None	N
R/N	0.4619	ambiguous	0.4948	ambiguous	-0.12	Destabilizing	0.072	N	0.263	neutral	None	None	None	None	N
R/P	0.9019	likely_pathogenic	0.9206	pathogenic	0.022	Stabilizing	0.356	N	0.421	neutral	None	None	None	None	N
R/Q	0.0906	likely_benign	0.1042	benign	-0.23	Destabilizing	0.001	N	0.123	neutral	None	None	None	None	N
R/S	0.4126	ambiguous	0.4724	ambiguous	-0.799	Destabilizing	0.012	N	0.341	neutral	N	0.439047328	None	None	N
R/T	0.2119	likely_benign	0.241	benign	-0.483	Destabilizing	0.055	N	0.397	neutral	N	0.480378183	None	None	N
R/V	0.3681	ambiguous	0.4247	ambiguous	0.022	Stabilizing	0.038	N	0.449	neutral	None	None	None	None	N
R/W	0.195	likely_benign	0.2267	benign	-0.041	Destabilizing	0.828	D	0.313	neutral	D	0.598822925	None	None	N
R/Y	0.3974	ambiguous	0.4688	ambiguous	0.251	Stabilizing	0.628	D	0.388	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.