TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16192	48799;48800;48801	chr2:178615371;178615370;178615369	chr2:179480098;179480097;179480096
N2AB	14551	43876;43877;43878	chr2:178615371;178615370;178615369	chr2:179480098;179480097;179480096
N2A	13624	41095;41096;41097	chr2:178615371;178615370;178615369	chr2:179480098;179480097;179480096
N2B	7127	21604;21605;21606	chr2:178615371;178615370;178615369	chr2:179480098;179480097;179480096
Novex-1	7252	21979;21980;21981	chr2:178615371;178615370;178615369	chr2:179480098;179480097;179480096
Novex-2	7319	22180;22181;22182	chr2:178615371;178615370;178615369	chr2:179480098;179480097;179480096
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: Fn3-5
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.144
• 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	rs2057142108	None	0.767	N	0.306	0.211	0.590228304998	gnomAD-4.0.0	1.59378E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86341E-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	0.773	likely_pathogenic	0.7155	pathogenic	-2.351	Highly Destabilizing	0.998	D	0.647	neutral	D	0.771270056	None	None	N
V/C	0.9648	likely_pathogenic	0.9664	pathogenic	-1.97	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/D	0.9988	likely_pathogenic	0.9985	pathogenic	-3.266	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.772706919	None	None	N
V/E	0.9945	likely_pathogenic	0.9932	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/F	0.9202	likely_pathogenic	0.9024	pathogenic	-1.319	Destabilizing	0.999	D	0.833	deleterious	D	0.736823898	None	None	N
V/G	0.9515	likely_pathogenic	0.9341	pathogenic	-2.948	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.772706919	None	None	N
V/H	0.9983	likely_pathogenic	0.9981	pathogenic	-2.776	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.0918	likely_benign	0.0939	benign	-0.647	Destabilizing	0.767	D	0.306	neutral	N	0.445233884	None	None	N
V/K	0.9947	likely_pathogenic	0.9928	pathogenic	-2.108	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/L	0.5664	likely_pathogenic	0.5556	ambiguous	-0.647	Destabilizing	0.981	D	0.594	neutral	N	0.493725807	None	None	N
V/M	0.7517	likely_pathogenic	0.732	pathogenic	-0.787	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/N	0.9955	likely_pathogenic	0.9951	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/P	0.9632	likely_pathogenic	0.9444	pathogenic	-1.192	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/Q	0.9922	likely_pathogenic	0.9902	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/R	0.9894	likely_pathogenic	0.9855	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/S	0.9716	likely_pathogenic	0.9644	pathogenic	-3.183	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/T	0.8315	likely_pathogenic	0.7902	pathogenic	-2.755	Highly Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9978	pathogenic	-1.925	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Y	0.9945	likely_pathogenic	0.9934	pathogenic	-1.56	Destabilizing	1.0	D	0.835	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.