TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23030	69313;69314;69315	chr2:178577247;178577246;178577245	chr2:179441974;179441973;179441972
N2AB	21389	64390;64391;64392	chr2:178577247;178577246;178577245	chr2:179441974;179441973;179441972
N2A	20462	61609;61610;61611	chr2:178577247;178577246;178577245	chr2:179441974;179441973;179441972
N2B	13965	42118;42119;42120	chr2:178577247;178577246;178577245	chr2:179441974;179441973;179441972
Novex-1	14090	42493;42494;42495	chr2:178577247;178577246;178577245	chr2:179441974;179441973;179441972
Novex-2	14157	42694;42695;42696	chr2:178577247;178577246;178577245	chr2:179441974;179441973;179441972
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-128
• Domain position: 81
• Structural Position: 168
• Q(SASA): 0.2596
• 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
V/L	rs1389259455	None	0.003	N	0.277	0.059	0.253726318573	gnomAD-4.0.0	1.59271E-06	None	None	None	None	N	None	5.66251E-05	0	None	0	0	None	0	0	0	0	0
V/M	rs1389259455	-0.449	0.196	N	0.419	0.091	0.278968121808	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/M	rs1389259455	-0.449	0.196	N	0.419	0.091	0.278968121808	gnomAD-4.0.0	1.59271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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
V/A	0.0726	likely_benign	0.069	benign	-0.926	Destabilizing	0.001	N	0.208	neutral	N	0.48322537	None	None	N
V/C	0.5425	ambiguous	0.5213	ambiguous	-0.46	Destabilizing	0.245	N	0.435	neutral	None	None	None	None	N
V/D	0.1295	likely_benign	0.0931	benign	-1.018	Destabilizing	None	N	0.395	neutral	None	None	None	None	N
V/E	0.0537	likely_benign	0.0504	benign	-1.121	Destabilizing	None	N	0.273	neutral	N	0.399489265	None	None	N
V/F	0.2108	likely_benign	0.1997	benign	-1.049	Destabilizing	0.085	N	0.513	neutral	None	None	None	None	N
V/G	0.1148	likely_benign	0.1043	benign	-1.115	Destabilizing	None	N	0.394	neutral	N	0.508699817	None	None	N
V/H	0.2901	likely_benign	0.2657	benign	-0.786	Destabilizing	0.138	N	0.581	neutral	None	None	None	None	N
V/I	0.0832	likely_benign	0.0794	benign	-0.552	Destabilizing	0.018	N	0.353	neutral	None	None	None	None	N
V/K	0.1027	likely_benign	0.097	benign	-0.84	Destabilizing	0.004	N	0.372	neutral	None	None	None	None	N
V/L	0.1487	likely_benign	0.1435	benign	-0.552	Destabilizing	0.003	N	0.277	neutral	N	0.485804315	None	None	N
V/M	0.0934	likely_benign	0.0934	benign	-0.301	Destabilizing	0.196	N	0.419	neutral	N	0.513894993	None	None	N
V/N	0.1154	likely_benign	0.097	benign	-0.43	Destabilizing	0.004	N	0.372	neutral	None	None	None	None	N
V/P	0.6384	likely_pathogenic	0.6321	pathogenic	-0.642	Destabilizing	0.018	N	0.398	neutral	None	None	None	None	N
V/Q	0.0794	likely_benign	0.0819	benign	-0.728	Destabilizing	None	N	0.298	neutral	None	None	None	None	N
V/R	0.13	likely_benign	0.1266	benign	-0.227	Destabilizing	0.009	N	0.397	neutral	None	None	None	None	N
V/S	0.078	likely_benign	0.0681	benign	-0.742	Destabilizing	None	N	0.303	neutral	None	None	None	None	N
V/T	0.0653	likely_benign	0.0625	benign	-0.758	Destabilizing	None	N	0.119	neutral	None	None	None	None	N
V/W	0.715	likely_pathogenic	0.6723	pathogenic	-1.166	Destabilizing	0.497	N	0.511	neutral	None	None	None	None	N
V/Y	0.399	ambiguous	0.3414	ambiguous	-0.894	Destabilizing	0.085	N	0.492	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.