TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22965	69118;69119;69120	chr2:178577442;178577441;178577440	chr2:179442169;179442168;179442167
N2AB	21324	64195;64196;64197	chr2:178577442;178577441;178577440	chr2:179442169;179442168;179442167
N2A	20397	61414;61415;61416	chr2:178577442;178577441;178577440	chr2:179442169;179442168;179442167
N2B	13900	41923;41924;41925	chr2:178577442;178577441;178577440	chr2:179442169;179442168;179442167
Novex-1	14025	42298;42299;42300	chr2:178577442;178577441;178577440	chr2:179442169;179442168;179442167
Novex-2	14092	42499;42500;42501	chr2:178577442;178577441;178577440	chr2:179442169;179442168;179442167
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-128
• Domain position: 16
• Structural Position: 29
• Q(SASA): 0.113
• 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/A	None	None	0.027	N	0.633	0.159	0.310147130316	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
V/A	0.1329	likely_benign	0.1223	benign	-1.386	Destabilizing	0.027	N	0.633	neutral	N	0.495670939	None	None	N
V/C	0.5648	likely_pathogenic	0.5206	ambiguous	-1.023	Destabilizing	0.935	D	0.662	neutral	None	None	None	None	N
V/D	0.2836	likely_benign	0.2784	benign	-1.107	Destabilizing	0.317	N	0.751	deleterious	N	0.460504734	None	None	N
V/E	0.1991	likely_benign	0.1979	benign	-1.081	Destabilizing	0.38	N	0.693	prob.neutral	None	None	None	None	N
V/F	0.1467	likely_benign	0.1302	benign	-0.967	Destabilizing	0.317	N	0.717	prob.delet.	N	0.463213759	None	None	N
V/G	0.1981	likely_benign	0.1946	benign	-1.726	Destabilizing	0.317	N	0.731	prob.delet.	N	0.490218784	None	None	N
V/H	0.3473	ambiguous	0.308	benign	-1.164	Destabilizing	0.824	D	0.729	prob.delet.	None	None	None	None	N
V/I	0.0729	likely_benign	0.0663	benign	-0.547	Destabilizing	None	N	0.365	neutral	N	0.472447363	None	None	N
V/K	0.192	likely_benign	0.1877	benign	-1.251	Destabilizing	0.081	N	0.692	prob.neutral	None	None	None	None	N
V/L	0.1349	likely_benign	0.1168	benign	-0.547	Destabilizing	None	N	0.279	neutral	N	0.485472588	None	None	N
V/M	0.109	likely_benign	0.0953	benign	-0.497	Destabilizing	0.38	N	0.661	neutral	None	None	None	None	N
V/N	0.1837	likely_benign	0.1608	benign	-1.119	Destabilizing	0.38	N	0.751	deleterious	None	None	None	None	N
V/P	0.767	likely_pathogenic	0.7415	pathogenic	-0.791	Destabilizing	0.555	D	0.706	prob.neutral	None	None	None	None	N
V/Q	0.1883	likely_benign	0.1872	benign	-1.222	Destabilizing	0.38	N	0.709	prob.delet.	None	None	None	None	N
V/R	0.1886	likely_benign	0.1859	benign	-0.755	Destabilizing	0.001	N	0.636	neutral	None	None	None	None	N
V/S	0.133	likely_benign	0.1238	benign	-1.667	Destabilizing	0.081	N	0.683	prob.neutral	None	None	None	None	N
V/T	0.1069	likely_benign	0.0954	benign	-1.517	Destabilizing	0.002	N	0.471	neutral	None	None	None	None	N
V/W	0.7455	likely_pathogenic	0.7043	pathogenic	-1.168	Destabilizing	0.935	D	0.748	deleterious	None	None	None	None	N
V/Y	0.3995	ambiguous	0.3527	ambiguous	-0.869	Destabilizing	0.555	D	0.711	prob.delet.	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.