TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32766	98521;98522;98523	chr2:178539769;178539768;178539767	chr2:179404496;179404495;179404494
N2AB	31125	93598;93599;93600	chr2:178539769;178539768;178539767	chr2:179404496;179404495;179404494
N2A	30198	90817;90818;90819	chr2:178539769;178539768;178539767	chr2:179404496;179404495;179404494
N2B	23701	71326;71327;71328	chr2:178539769;178539768;178539767	chr2:179404496;179404495;179404494
Novex-1	23826	71701;71702;71703	chr2:178539769;178539768;178539767	chr2:179404496;179404495;179404494
Novex-2	23893	71902;71903;71904	chr2:178539769;178539768;178539767	chr2:179404496;179404495;179404494
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-155
• Domain position: 59
• Structural Position: 145
• Q(SASA): 0.5658
• 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/Y	rs727504449	-0.386	0.627	N	0.423	0.319	0.627368885312	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	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	0.1243	likely_benign	0.1174	benign	-0.385	Destabilizing	0.09	N	0.366	neutral	N	0.472067013	None	None	N
D/C	0.4004	ambiguous	0.3702	ambiguous	0.067	Stabilizing	0.944	D	0.422	neutral	None	None	None	None	N
D/E	0.104	likely_benign	0.1064	benign	-0.611	Destabilizing	0.001	N	0.179	neutral	N	0.400569488	None	None	N
D/F	0.3854	ambiguous	0.3684	ambiguous	-0.444	Destabilizing	0.69	D	0.423	neutral	None	None	None	None	N
D/G	0.1388	likely_benign	0.1324	benign	-0.64	Destabilizing	0.324	N	0.319	neutral	N	0.507950456	None	None	N
D/H	0.1661	likely_benign	0.1569	benign	-0.655	Destabilizing	0.001	N	0.199	neutral	N	0.466815909	None	None	N
D/I	0.2034	likely_benign	0.191	benign	0.251	Stabilizing	0.098	N	0.411	neutral	None	None	None	None	N
D/K	0.1931	likely_benign	0.1885	benign	0.015	Stabilizing	0.241	N	0.305	neutral	None	None	None	None	N
D/L	0.1947	likely_benign	0.1831	benign	0.251	Stabilizing	0.241	N	0.391	neutral	None	None	None	None	N
D/M	0.3684	ambiguous	0.3375	benign	0.656	Stabilizing	0.69	D	0.415	neutral	None	None	None	None	N
D/N	0.0758	likely_benign	0.0737	benign	-0.279	Destabilizing	0.324	N	0.243	neutral	N	0.445939205	None	None	N
D/P	0.8051	likely_pathogenic	0.7955	pathogenic	0.063	Stabilizing	0.818	D	0.351	neutral	None	None	None	None	N
D/Q	0.1747	likely_benign	0.1686	benign	-0.227	Destabilizing	0.241	N	0.32	neutral	None	None	None	None	N
D/R	0.2351	likely_benign	0.2247	benign	0.063	Stabilizing	0.69	D	0.378	neutral	None	None	None	None	N
D/S	0.0897	likely_benign	0.0846	benign	-0.424	Destabilizing	0.241	N	0.218	neutral	None	None	None	None	N
D/T	0.1459	likely_benign	0.1267	benign	-0.227	Destabilizing	0.241	N	0.295	neutral	None	None	None	None	N
D/V	0.126	likely_benign	0.1209	benign	0.063	Stabilizing	0.001	N	0.289	neutral	N	0.461428732	None	None	N
D/W	0.7582	likely_pathogenic	0.7484	pathogenic	-0.366	Destabilizing	0.981	D	0.527	neutral	None	None	None	None	N
D/Y	0.177	likely_benign	0.1717	benign	-0.226	Destabilizing	0.627	D	0.423	neutral	N	0.500659124	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.