TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35202	105829;105830;105831	chr2:178531011;178531010;178531009	chr2:179395738;179395737;179395736
N2AB	33561	100906;100907;100908	chr2:178531011;178531010;178531009	chr2:179395738;179395737;179395736
N2A	32634	98125;98126;98127	chr2:178531011;178531010;178531009	chr2:179395738;179395737;179395736
N2B	26137	78634;78635;78636	chr2:178531011;178531010;178531009	chr2:179395738;179395737;179395736
Novex-1	26262	79009;79010;79011	chr2:178531011;178531010;178531009	chr2:179395738;179395737;179395736
Novex-2	26329	79210;79211;79212	chr2:178531011;178531010;178531009	chr2:179395738;179395737;179395736
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-164
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2462
• 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/M	None	None	0.969	N	0.808	0.326	0.637791279193	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	0.1854	likely_benign	0.2122	benign	-1.965	Destabilizing	0.899	D	0.62	neutral	N	0.500215867	None	None	N
V/C	0.8194	likely_pathogenic	0.8423	pathogenic	-1.568	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/D	0.5897	likely_pathogenic	0.6197	pathogenic	-2.354	Highly Destabilizing	0.996	D	0.87	deleterious	None	None	None	None	N
V/E	0.316	likely_benign	0.3517	ambiguous	-2.262	Highly Destabilizing	0.984	D	0.818	deleterious	D	0.530229883	None	None	N
V/F	0.2134	likely_benign	0.2287	benign	-1.247	Destabilizing	0.976	D	0.832	deleterious	None	None	None	None	N
V/G	0.4025	ambiguous	0.4432	ambiguous	-2.361	Highly Destabilizing	0.984	D	0.826	deleterious	D	0.530690386	None	None	N
V/H	0.6027	likely_pathogenic	0.6178	pathogenic	-1.833	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/I	0.0853	likely_benign	0.0838	benign	-0.917	Destabilizing	0.709	D	0.596	neutral	None	None	None	None	N
V/K	0.3205	likely_benign	0.3394	benign	-1.641	Destabilizing	0.988	D	0.819	deleterious	None	None	None	None	N
V/L	0.1803	likely_benign	0.1898	benign	-0.917	Destabilizing	0.027	N	0.356	neutral	N	0.505046224	None	None	N
V/M	0.139	likely_benign	0.147	benign	-0.951	Destabilizing	0.969	D	0.808	deleterious	N	0.489722162	None	None	N
V/N	0.476	ambiguous	0.4687	ambiguous	-1.665	Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
V/P	0.9752	likely_pathogenic	0.9797	pathogenic	-1.237	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
V/Q	0.3263	likely_benign	0.3392	benign	-1.745	Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
V/R	0.2525	likely_benign	0.2803	benign	-1.182	Destabilizing	0.988	D	0.877	deleterious	None	None	None	None	N
V/S	0.2816	likely_benign	0.297	benign	-2.22	Highly Destabilizing	0.988	D	0.809	deleterious	None	None	None	None	N
V/T	0.1646	likely_benign	0.1765	benign	-2.021	Highly Destabilizing	0.922	D	0.637	neutral	None	None	None	None	N
V/W	0.7835	likely_pathogenic	0.8264	pathogenic	-1.549	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/Y	0.6398	likely_pathogenic	0.6633	pathogenic	-1.264	Destabilizing	0.988	D	0.849	deleterious	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.