TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17234	51925;51926;51927	chr2:178609723;178609722;178609721	chr2:179474450;179474449;179474448
N2AB	15593	47002;47003;47004	chr2:178609723;178609722;178609721	chr2:179474450;179474449;179474448
N2A	14666	44221;44222;44223	chr2:178609723;178609722;178609721	chr2:179474450;179474449;179474448
N2B	8169	24730;24731;24732	chr2:178609723;178609722;178609721	chr2:179474450;179474449;179474448
Novex-1	8294	25105;25106;25107	chr2:178609723;178609722;178609721	chr2:179474450;179474449;179474448
Novex-2	8361	25306;25307;25308	chr2:178609723;178609722;178609721	chr2:179474450;179474449;179474448
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-13
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.15
• 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
S/A	None	None	0.863	N	0.819	0.436	0.256793551483	gnomAD-4.0.0	3.20818E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.88401E-05	0
S/Y	rs768996750	-0.566	0.997	D	0.905	0.631	0.812414231654	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	5.59E-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
S/A	0.4297	ambiguous	0.3661	ambiguous	-0.605	Destabilizing	0.863	D	0.819	deleterious	N	0.497892598	None	None	N
S/C	0.2815	likely_benign	0.2935	benign	-0.543	Destabilizing	0.999	D	0.83	deleterious	D	0.555207557	None	None	N
S/D	0.9944	likely_pathogenic	0.9915	pathogenic	-0.995	Destabilizing	0.953	D	0.859	deleterious	None	None	None	None	N
S/E	0.9948	likely_pathogenic	0.9926	pathogenic	-0.921	Destabilizing	0.91	D	0.842	deleterious	None	None	None	None	N
S/F	0.9897	likely_pathogenic	0.9839	pathogenic	-0.383	Destabilizing	0.997	D	0.904	deleterious	D	0.555207557	None	None	N
S/G	0.5206	ambiguous	0.4774	ambiguous	-0.933	Destabilizing	0.953	D	0.838	deleterious	None	None	None	None	N
S/H	0.9836	likely_pathogenic	0.9779	pathogenic	-1.43	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
S/I	0.96	likely_pathogenic	0.9405	pathogenic	0.183	Stabilizing	0.993	D	0.895	deleterious	None	None	None	None	N
S/K	0.9984	likely_pathogenic	0.9977	pathogenic	-0.975	Destabilizing	0.06	N	0.628	neutral	None	None	None	None	N
S/L	0.919	likely_pathogenic	0.8907	pathogenic	0.183	Stabilizing	0.953	D	0.885	deleterious	None	None	None	None	N
S/M	0.9546	likely_pathogenic	0.9399	pathogenic	0.256	Stabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
S/N	0.9463	likely_pathogenic	0.9328	pathogenic	-1.136	Destabilizing	0.953	D	0.862	deleterious	None	None	None	None	N
S/P	0.9915	likely_pathogenic	0.9864	pathogenic	-0.044	Destabilizing	0.991	D	0.865	deleterious	D	0.554954068	None	None	N
S/Q	0.9867	likely_pathogenic	0.9829	pathogenic	-1.105	Destabilizing	0.986	D	0.861	deleterious	None	None	None	None	N
S/R	0.9942	likely_pathogenic	0.9919	pathogenic	-1.037	Destabilizing	0.973	D	0.864	deleterious	None	None	None	None	N
S/T	0.6107	likely_pathogenic	0.5299	ambiguous	-0.944	Destabilizing	0.939	D	0.848	deleterious	N	0.506322388	None	None	N
S/V	0.9002	likely_pathogenic	0.8602	pathogenic	-0.044	Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
S/W	0.9918	likely_pathogenic	0.9872	pathogenic	-0.538	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
S/Y	0.9849	likely_pathogenic	0.9766	pathogenic	-0.23	Destabilizing	0.997	D	0.905	deleterious	D	0.554954068	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.