TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35665	107218;107219;107220	chr2:178528758;178528757;178528756	chr2:179393485;179393484;179393483
N2AB	34024	102295;102296;102297	chr2:178528758;178528757;178528756	chr2:179393485;179393484;179393483
N2A	33097	99514;99515;99516	chr2:178528758;178528757;178528756	chr2:179393485;179393484;179393483
N2B	26600	80023;80024;80025	chr2:178528758;178528757;178528756	chr2:179393485;179393484;179393483
Novex-1	26725	80398;80399;80400	chr2:178528758;178528757;178528756	chr2:179393485;179393484;179393483
Novex-2	26792	80599;80600;80601	chr2:178528758;178528757;178528756	chr2:179393485;179393484;179393483
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-167
• Domain position: 59
• Structural Position: 141
• Q(SASA): 0.3869
• 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
K/R	rs746841189	-0.269	0.001	N	0.228	0.085	0.221019684889	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	8.28E-05	0	None	0	0	None	0	None	0	0	0
K/R	rs746841189	-0.269	0.001	N	0.228	0.085	0.221019684889	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs746841189	-0.269	0.001	N	0.228	0.085	0.221019684889	gnomAD-4.0.0	5.12888E-06	None	None	None	None	N	None	6.76361E-05	0	None	0	0	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
K/A	0.6294	likely_pathogenic	0.5564	ambiguous	-0.332	Destabilizing	0.272	N	0.609	neutral	None	None	None	None	N
K/C	0.8683	likely_pathogenic	0.8308	pathogenic	-0.457	Destabilizing	0.968	D	0.722	prob.delet.	None	None	None	None	N
K/D	0.7921	likely_pathogenic	0.776	pathogenic	-0.128	Destabilizing	0.567	D	0.667	neutral	None	None	None	None	N
K/E	0.3296	likely_benign	0.302	benign	-0.049	Destabilizing	0.124	N	0.525	neutral	N	0.478878343	None	None	N
K/F	0.8766	likely_pathogenic	0.8371	pathogenic	-0.107	Destabilizing	0.567	D	0.732	prob.delet.	None	None	None	None	N
K/G	0.66	likely_pathogenic	0.6038	pathogenic	-0.671	Destabilizing	0.272	N	0.671	neutral	None	None	None	None	N
K/H	0.4377	ambiguous	0.3771	ambiguous	-1.064	Destabilizing	0.909	D	0.693	prob.neutral	None	None	None	None	N
K/I	0.5703	likely_pathogenic	0.5024	ambiguous	0.527	Stabilizing	0.396	N	0.679	prob.neutral	None	None	None	None	N
K/L	0.5244	ambiguous	0.4575	ambiguous	0.527	Stabilizing	0.072	N	0.611	neutral	None	None	None	None	N
K/M	0.418	ambiguous	0.3652	ambiguous	0.406	Stabilizing	0.025	N	0.427	neutral	N	0.462199523	None	None	N
K/N	0.5738	likely_pathogenic	0.5448	ambiguous	-0.294	Destabilizing	0.497	N	0.561	neutral	N	0.479745134	None	None	N
K/P	0.8461	likely_pathogenic	0.8392	pathogenic	0.272	Stabilizing	0.726	D	0.711	prob.delet.	None	None	None	None	N
K/Q	0.1927	likely_benign	0.1618	benign	-0.435	Destabilizing	0.22	N	0.562	neutral	N	0.478358268	None	None	N
K/R	0.1068	likely_benign	0.0932	benign	-0.537	Destabilizing	0.001	N	0.228	neutral	N	0.479225059	None	None	N
K/S	0.5967	likely_pathogenic	0.5492	ambiguous	-0.898	Destabilizing	0.272	N	0.491	neutral	None	None	None	None	N
K/T	0.3384	likely_benign	0.2953	benign	-0.631	Destabilizing	0.22	N	0.649	neutral	N	0.479571776	None	None	N
K/V	0.6172	likely_pathogenic	0.5343	ambiguous	0.272	Stabilizing	0.157	N	0.664	neutral	None	None	None	None	N
K/W	0.8716	likely_pathogenic	0.83	pathogenic	0.002	Stabilizing	0.968	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.7595	likely_pathogenic	0.6979	pathogenic	0.304	Stabilizing	0.726	D	0.736	prob.delet.	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.