TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10017	30274;30275;30276	chr2:178704321;178704320;178704319	chr2:179569048;179569047;179569046
N2AB	9700	29323;29324;29325	chr2:178704321;178704320;178704319	chr2:179569048;179569047;179569046
N2A	8773	26542;26543;26544	chr2:178704321;178704320;178704319	chr2:179569048;179569047;179569046
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-85
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.1864
• 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	0.026	None	0.253	0.197	0.415820034956	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.3613	ambiguous	0.4874	ambiguous	-1.604	Destabilizing	0.026	N	0.347	neutral	None	None	None	None	N
V/C	0.9063	likely_pathogenic	0.9372	pathogenic	-0.846	Destabilizing	0.997	D	0.595	neutral	None	None	None	None	N
V/D	0.9268	likely_pathogenic	0.9508	pathogenic	-1.501	Destabilizing	0.988	D	0.687	prob.neutral	None	None	None	None	N
V/E	0.7835	likely_pathogenic	0.8373	pathogenic	-1.384	Destabilizing	0.968	D	0.615	neutral	None	None	None	None	N
V/F	0.6666	likely_pathogenic	0.7146	pathogenic	-1.029	Destabilizing	0.976	D	0.631	neutral	None	None	None	None	N
V/G	0.6167	likely_pathogenic	0.7044	pathogenic	-2.017	Highly Destabilizing	0.938	D	0.638	neutral	None	None	None	None	N
V/H	0.9502	likely_pathogenic	0.9653	pathogenic	-1.487	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
V/I	0.1365	likely_benign	0.1396	benign	-0.51	Destabilizing	0.026	N	0.299	neutral	None	None	None	None	N
V/K	0.8342	likely_pathogenic	0.8651	pathogenic	-1.153	Destabilizing	0.976	D	0.613	neutral	None	None	None	None	N
V/L	0.6179	likely_pathogenic	0.6565	pathogenic	-0.51	Destabilizing	0.026	N	0.253	neutral	None	None	None	None	N
V/M	0.4307	ambiguous	0.4939	ambiguous	-0.395	Destabilizing	0.976	D	0.508	neutral	None	None	None	None	N
V/N	0.8669	likely_pathogenic	0.9017	pathogenic	-1.141	Destabilizing	0.988	D	0.695	prob.neutral	None	None	None	None	N
V/P	0.9755	likely_pathogenic	0.9767	pathogenic	-0.844	Destabilizing	0.988	D	0.641	neutral	None	None	None	None	N
V/Q	0.7819	likely_pathogenic	0.834	pathogenic	-1.146	Destabilizing	0.988	D	0.653	neutral	None	None	None	None	N
V/R	0.7722	likely_pathogenic	0.8083	pathogenic	-0.843	Destabilizing	0.988	D	0.695	prob.neutral	None	None	None	None	N
V/S	0.6163	likely_pathogenic	0.7208	pathogenic	-1.725	Destabilizing	0.952	D	0.583	neutral	None	None	None	None	N
V/T	0.4719	ambiguous	0.5928	pathogenic	-1.476	Destabilizing	0.919	D	0.545	neutral	None	None	None	None	N
V/W	0.9866	likely_pathogenic	0.9897	pathogenic	-1.331	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
V/Y	0.9426	likely_pathogenic	0.9546	pathogenic	-0.971	Destabilizing	0.996	D	0.624	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.