TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17607	53044;53045;53046	chr2:178607968;178607967;178607966	chr2:179472695;179472694;179472693
N2AB	15966	48121;48122;48123	chr2:178607968;178607967;178607966	chr2:179472695;179472694;179472693
N2A	15039	45340;45341;45342	chr2:178607968;178607967;178607966	chr2:179472695;179472694;179472693
N2B	8542	25849;25850;25851	chr2:178607968;178607967;178607966	chr2:179472695;179472694;179472693
Novex-1	8667	26224;26225;26226	chr2:178607968;178607967;178607966	chr2:179472695;179472694;179472693
Novex-2	8734	26425;26426;26427	chr2:178607968;178607967;178607966	chr2:179472695;179472694;179472693
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-16
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1903
• 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
D/H	rs1381094642	-0.903	0.638	N	0.799	0.248	0.203808441222	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	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
D/A	0.2949	likely_benign	0.3047	benign	-2.122	Highly Destabilizing	0.334	N	0.705	prob.neutral	N	0.48096389	None	None	N
D/C	0.5102	ambiguous	0.52	ambiguous	-1.26	Destabilizing	0.982	D	0.799	deleterious	None	None	None	None	N
D/E	0.2186	likely_benign	0.2239	benign	-0.863	Destabilizing	0.504	D	0.626	neutral	N	0.347838576	None	None	N
D/F	0.2969	likely_benign	0.2872	benign	-2.104	Highly Destabilizing	0.539	D	0.773	deleterious	None	None	None	None	N
D/G	0.4058	ambiguous	0.4074	ambiguous	-2.454	Highly Destabilizing	0.504	D	0.693	prob.neutral	D	0.522540614	None	None	N
D/H	0.2036	likely_benign	0.2139	benign	-1.924	Destabilizing	0.638	D	0.799	deleterious	N	0.514209133	None	None	N
D/I	0.5757	likely_pathogenic	0.5421	ambiguous	-1.188	Destabilizing	0.7	D	0.802	deleterious	None	None	None	None	N
D/K	0.6227	likely_pathogenic	0.6454	pathogenic	-1.907	Destabilizing	0.7	D	0.768	deleterious	None	None	None	None	N
D/L	0.4487	ambiguous	0.4474	ambiguous	-1.188	Destabilizing	0.539	D	0.76	deleterious	None	None	None	None	N
D/M	0.7065	likely_pathogenic	0.6746	pathogenic	-0.428	Destabilizing	0.947	D	0.804	deleterious	None	None	None	None	N
D/N	0.1616	likely_benign	0.1526	benign	-1.85	Destabilizing	0.781	D	0.771	deleterious	N	0.482484827	None	None	N
D/P	0.9871	likely_pathogenic	0.9874	pathogenic	-1.485	Destabilizing	0.935	D	0.795	deleterious	None	None	None	None	N
D/Q	0.3921	ambiguous	0.4015	ambiguous	-1.626	Destabilizing	0.826	D	0.809	deleterious	None	None	None	None	N
D/R	0.5946	likely_pathogenic	0.6075	pathogenic	-1.709	Destabilizing	0.7	D	0.803	deleterious	None	None	None	None	N
D/S	0.1765	likely_benign	0.1838	benign	-2.605	Highly Destabilizing	0.399	N	0.727	prob.delet.	None	None	None	None	N
D/T	0.4245	ambiguous	0.4253	ambiguous	-2.286	Highly Destabilizing	0.7	D	0.759	deleterious	None	None	None	None	N
D/V	0.375	ambiguous	0.3468	ambiguous	-1.485	Destabilizing	0.638	D	0.773	deleterious	N	0.470203469	None	None	N
D/W	0.7354	likely_pathogenic	0.7155	pathogenic	-2.139	Highly Destabilizing	0.947	D	0.804	deleterious	None	None	None	None	N
D/Y	0.0716	likely_benign	0.075	benign	-1.945	Destabilizing	0.002	N	0.614	neutral	N	0.463108309	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.