TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14910	44953;44954;44955	chr2:178624552;178624551;178624550	chr2:179489279;179489278;179489277
N2AB	13269	40030;40031;40032	chr2:178624552;178624551;178624550	chr2:179489279;179489278;179489277
N2A	12342	37249;37250;37251	chr2:178624552;178624551;178624550	chr2:179489279;179489278;179489277
N2B	5845	17758;17759;17760	chr2:178624552;178624551;178624550	chr2:179489279;179489278;179489277
Novex-1	5970	18133;18134;18135	chr2:178624552;178624551;178624550	chr2:179489279;179489278;179489277
Novex-2	6037	18334;18335;18336	chr2:178624552;178624551;178624550	chr2:179489279;179489278;179489277
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-100
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.1578
• 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	None	None	None	N	0.237	0.132	0.441949972293	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
V/A	0.4083	ambiguous	0.39	ambiguous	-2.184	Highly Destabilizing	0.052	N	0.585	neutral	D	0.552898589	None	None	N
V/C	0.7752	likely_pathogenic	0.7036	pathogenic	-1.565	Destabilizing	0.935	D	0.612	neutral	None	None	None	None	N
V/D	0.6696	likely_pathogenic	0.6214	pathogenic	-2.733	Highly Destabilizing	0.484	N	0.69	prob.neutral	D	0.577890796	None	None	N
V/E	0.4422	ambiguous	0.4266	ambiguous	-2.578	Highly Destabilizing	0.555	D	0.642	neutral	None	None	None	None	N
V/F	0.1857	likely_benign	0.1595	benign	-1.346	Destabilizing	0.317	N	0.655	neutral	D	0.544891379	None	None	N
V/G	0.5651	likely_pathogenic	0.5137	ambiguous	-2.656	Highly Destabilizing	0.484	N	0.681	prob.neutral	D	0.703658959	None	None	N
V/H	0.558	ambiguous	0.4754	ambiguous	-2.352	Highly Destabilizing	0.935	D	0.655	neutral	None	None	None	None	N
V/I	0.0564	likely_benign	0.0527	benign	-0.888	Destabilizing	None	N	0.185	neutral	N	0.461997609	None	None	N
V/K	0.4019	ambiguous	0.3597	ambiguous	-1.955	Destabilizing	0.555	D	0.64	neutral	None	None	None	None	N
V/L	0.1448	likely_benign	0.113	benign	-0.888	Destabilizing	None	N	0.237	neutral	N	0.510168819	None	None	N
V/M	0.1733	likely_benign	0.1437	benign	-0.765	Destabilizing	0.38	N	0.659	neutral	None	None	None	None	N
V/N	0.4038	ambiguous	0.3358	benign	-2.08	Highly Destabilizing	0.791	D	0.687	prob.neutral	None	None	None	None	N
V/P	0.963	likely_pathogenic	0.9498	pathogenic	-1.293	Destabilizing	0.791	D	0.646	neutral	None	None	None	None	N
V/Q	0.4268	ambiguous	0.3786	ambiguous	-2.029	Highly Destabilizing	0.791	D	0.613	neutral	None	None	None	None	N
V/R	0.311	likely_benign	0.2759	benign	-1.59	Destabilizing	0.555	D	0.691	prob.neutral	None	None	None	None	N
V/S	0.427	ambiguous	0.3885	ambiguous	-2.645	Highly Destabilizing	0.262	N	0.647	neutral	None	None	None	None	N
V/T	0.3069	likely_benign	0.2994	benign	-2.373	Highly Destabilizing	0.149	N	0.623	neutral	None	None	None	None	N
V/W	0.816	likely_pathogenic	0.7586	pathogenic	-1.845	Destabilizing	0.935	D	0.679	prob.neutral	None	None	None	None	N
V/Y	0.5346	ambiguous	0.4561	ambiguous	-1.524	Destabilizing	0.555	D	0.653	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.