TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23474	70645;70646;70647	chr2:178575712;178575711;178575710	chr2:179440439;179440438;179440437
N2AB	21833	65722;65723;65724	chr2:178575712;178575711;178575710	chr2:179440439;179440438;179440437
N2A	20906	62941;62942;62943	chr2:178575712;178575711;178575710	chr2:179440439;179440438;179440437
N2B	14409	43450;43451;43452	chr2:178575712;178575711;178575710	chr2:179440439;179440438;179440437
Novex-1	14534	43825;43826;43827	chr2:178575712;178575711;178575710	chr2:179440439;179440438;179440437
Novex-2	14601	44026;44027;44028	chr2:178575712;178575711;178575710	chr2:179440439;179440438;179440437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-58
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2639
• 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/E	None	None	0.982	N	0.699	0.445	0.329540904979	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8591E-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
K/A	0.9551	likely_pathogenic	0.9657	pathogenic	-1.465	Destabilizing	0.996	D	0.694	prob.neutral	None	None	None	None	N
K/C	0.8687	likely_pathogenic	0.8977	pathogenic	-1.372	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/D	0.9957	likely_pathogenic	0.9968	pathogenic	-1.604	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
K/E	0.8982	likely_pathogenic	0.9235	pathogenic	-1.29	Destabilizing	0.982	D	0.699	prob.neutral	N	0.509565531	None	None	N
K/F	0.9669	likely_pathogenic	0.9712	pathogenic	-0.753	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
K/G	0.9752	likely_pathogenic	0.9823	pathogenic	-1.967	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/H	0.753	likely_pathogenic	0.771	pathogenic	-1.686	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/I	0.7851	likely_pathogenic	0.8145	pathogenic	-0.036	Destabilizing	0.975	D	0.857	deleterious	N	0.467214501	None	None	N
K/L	0.7889	likely_pathogenic	0.8213	pathogenic	-0.036	Destabilizing	0.962	D	0.773	deleterious	None	None	None	None	N
K/M	0.5751	likely_pathogenic	0.6125	pathogenic	-0.309	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/N	0.9745	likely_pathogenic	0.981	pathogenic	-1.631	Destabilizing	0.998	D	0.821	deleterious	D	0.536063577	None	None	N
K/P	0.9991	likely_pathogenic	0.9994	pathogenic	-0.492	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
K/Q	0.4919	ambiguous	0.5377	ambiguous	-1.285	Destabilizing	0.987	D	0.823	deleterious	N	0.496563384	None	None	N
K/R	0.1305	likely_benign	0.1413	benign	-0.664	Destabilizing	0.198	N	0.388	neutral	N	0.49383386	None	None	N
K/S	0.9676	likely_pathogenic	0.9773	pathogenic	-2.279	Highly Destabilizing	0.996	D	0.735	prob.delet.	None	None	None	None	N
K/T	0.8161	likely_pathogenic	0.8472	pathogenic	-1.684	Destabilizing	0.995	D	0.787	deleterious	N	0.495295936	None	None	N
K/V	0.7535	likely_pathogenic	0.7813	pathogenic	-0.492	Destabilizing	0.985	D	0.819	deleterious	None	None	None	None	N
K/W	0.9495	likely_pathogenic	0.9578	pathogenic	-0.7	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/Y	0.8988	likely_pathogenic	0.907	pathogenic	-0.384	Destabilizing	0.996	D	0.859	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.