TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13979	42160;42161;42162	chr2:178635254;178635253;178635252	chr2:179499981;179499980;179499979
N2AB	12338	37237;37238;37239	chr2:178635254;178635253;178635252	chr2:179499981;179499980;179499979
N2A	11411	34456;34457;34458	chr2:178635254;178635253;178635252	chr2:179499981;179499980;179499979
N2B	4914	14965;14966;14967	chr2:178635254;178635253;178635252	chr2:179499981;179499980;179499979
Novex-1	5039	15340;15341;15342	chr2:178635254;178635253;178635252	chr2:179499981;179499980;179499979
Novex-2	5106	15541;15542;15543	chr2:178635254;178635253;178635252	chr2:179499981;179499980;179499979
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: Ig-90
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.6959
• 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	rs1559980687	None	0.997	N	0.667	0.225	0.262662153117	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
K/R	rs1559980687	None	0.997	N	0.667	0.225	0.262662153117	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	2.78102E-05	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	0.8983	likely_pathogenic	0.8869	pathogenic	0.056	Stabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
K/C	0.9702	likely_pathogenic	0.9661	pathogenic	-0.104	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
K/D	0.8798	likely_pathogenic	0.8489	pathogenic	0.041	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
K/E	0.7577	likely_pathogenic	0.7141	pathogenic	0.064	Stabilizing	0.997	D	0.737	deleterious	N	0.444878128	None	None	N
K/F	0.9786	likely_pathogenic	0.9771	pathogenic	-0.01	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/G	0.618	likely_pathogenic	0.6121	pathogenic	-0.182	Destabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	N
K/H	0.7207	likely_pathogenic	0.7088	pathogenic	-0.451	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/I	0.9672	likely_pathogenic	0.9626	pathogenic	0.612	Stabilizing	0.999	D	0.81	deleterious	N	0.487090979	None	None	N
K/L	0.8743	likely_pathogenic	0.864	pathogenic	0.612	Stabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	N
K/M	0.7516	likely_pathogenic	0.7268	pathogenic	0.328	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/N	0.7388	likely_pathogenic	0.7175	pathogenic	0.248	Stabilizing	0.999	D	0.831	deleterious	N	0.443284162	None	None	N
K/P	0.9895	likely_pathogenic	0.9886	pathogenic	0.456	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/Q	0.5343	ambiguous	0.5267	ambiguous	0.096	Stabilizing	0.999	D	0.851	deleterious	N	0.485127007	None	None	N
K/R	0.1984	likely_benign	0.1951	benign	-0.074	Destabilizing	0.997	D	0.667	prob.neutral	N	0.432381208	None	None	N
K/S	0.8887	likely_pathogenic	0.8806	pathogenic	-0.224	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
K/T	0.768	likely_pathogenic	0.7673	pathogenic	-0.046	Destabilizing	0.999	D	0.777	deleterious	N	0.434635182	None	None	N
K/V	0.9428	likely_pathogenic	0.9375	pathogenic	0.456	Stabilizing	0.999	D	0.737	deleterious	None	None	None	None	N
K/W	0.9737	likely_pathogenic	0.9675	pathogenic	-0.021	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/Y	0.9258	likely_pathogenic	0.9139	pathogenic	0.313	Stabilizing	1.0	D	0.803	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.