TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21881	65866;65867;65868	chr2:178583162;178583161;178583160	chr2:179447889;179447888;179447887
N2AB	20240	60943;60944;60945	chr2:178583162;178583161;178583160	chr2:179447889;179447888;179447887
N2A	19313	58162;58163;58164	chr2:178583162;178583161;178583160	chr2:179447889;179447888;179447887
N2B	12816	38671;38672;38673	chr2:178583162;178583161;178583160	chr2:179447889;179447888;179447887
Novex-1	12941	39046;39047;39048	chr2:178583162;178583161;178583160	chr2:179447889;179447888;179447887
Novex-2	13008	39247;39248;39249	chr2:178583162;178583161;178583160	chr2:179447889;179447888;179447887
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-125
• Domain position: 16
• Structural Position: 28
• Q(SASA): 0.2023
• 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/I	rs2048158177	None	0.025	N	0.206	0.128	0.326616659874	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs2048158177	None	0.025	N	0.206	0.128	0.326616659874	gnomAD-4.0.0	6.57756E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47115E-05	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	0.4989	ambiguous	0.4949	ambiguous	-1.857	Destabilizing	0.892	D	0.557	neutral	N	0.474738306	None	None	N
V/C	0.877	likely_pathogenic	0.8737	pathogenic	-1.579	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
V/D	0.9866	likely_pathogenic	0.9812	pathogenic	-1.622	Destabilizing	0.994	D	0.827	deleterious	N	0.514811634	None	None	N
V/E	0.9646	likely_pathogenic	0.957	pathogenic	-1.507	Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
V/F	0.6032	likely_pathogenic	0.5311	ambiguous	-1.223	Destabilizing	0.967	D	0.805	deleterious	N	0.467536307	None	None	N
V/G	0.835	likely_pathogenic	0.801	pathogenic	-2.305	Highly Destabilizing	0.983	D	0.821	deleterious	N	0.480071155	None	None	N
V/H	0.9819	likely_pathogenic	0.9757	pathogenic	-1.765	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
V/I	0.0968	likely_benign	0.0918	benign	-0.672	Destabilizing	0.025	N	0.206	neutral	N	0.49093991	None	None	N
V/K	0.9616	likely_pathogenic	0.952	pathogenic	-1.667	Destabilizing	0.987	D	0.807	deleterious	None	None	None	None	N
V/L	0.5212	ambiguous	0.4603	ambiguous	-0.672	Destabilizing	0.369	N	0.475	neutral	N	0.479048048	None	None	N
V/M	0.4906	ambiguous	0.431	ambiguous	-0.66	Destabilizing	0.975	D	0.704	prob.neutral	None	None	None	None	N
V/N	0.9669	likely_pathogenic	0.9545	pathogenic	-1.727	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
V/P	0.9923	likely_pathogenic	0.9913	pathogenic	-1.033	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	N
V/Q	0.9523	likely_pathogenic	0.9392	pathogenic	-1.699	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
V/R	0.9431	likely_pathogenic	0.9282	pathogenic	-1.292	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
V/S	0.8802	likely_pathogenic	0.8557	pathogenic	-2.398	Highly Destabilizing	0.987	D	0.801	deleterious	None	None	None	None	N
V/T	0.6873	likely_pathogenic	0.6373	pathogenic	-2.131	Highly Destabilizing	0.916	D	0.643	neutral	None	None	None	None	N
V/W	0.9908	likely_pathogenic	0.987	pathogenic	-1.49	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
V/Y	0.9406	likely_pathogenic	0.9271	pathogenic	-1.176	Destabilizing	0.987	D	0.794	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.