TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31447	94564;94565;94566	chr2:178547186;178547185;178547184	chr2:179411913;179411912;179411911
N2AB	29806	89641;89642;89643	chr2:178547186;178547185;178547184	chr2:179411913;179411912;179411911
N2A	28879	86860;86861;86862	chr2:178547186;178547185;178547184	chr2:179411913;179411912;179411911
N2B	22382	67369;67370;67371	chr2:178547186;178547185;178547184	chr2:179411913;179411912;179411911
Novex-1	22507	67744;67745;67746	chr2:178547186;178547185;178547184	chr2:179411913;179411912;179411911
Novex-2	22574	67945;67946;67947	chr2:178547186;178547185;178547184	chr2:179411913;179411912;179411911
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: Fn3-117
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1951
• 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/N	rs1169915824	-2.251	0.993	N	0.799	0.368	0.346315397577	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs1169915824	-2.251	0.993	N	0.799	0.368	0.346315397577	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	2.28634E-05	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	0.9432	likely_pathogenic	0.9211	pathogenic	-1.472	Destabilizing	0.983	D	0.672	neutral	None	None	None	None	N
K/C	0.8493	likely_pathogenic	0.8104	pathogenic	-1.571	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
K/D	0.9961	likely_pathogenic	0.9938	pathogenic	-2.476	Highly Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
K/E	0.8999	likely_pathogenic	0.8715	pathogenic	-2.145	Highly Destabilizing	0.977	D	0.649	neutral	N	0.495082127	None	None	N
K/F	0.9676	likely_pathogenic	0.9602	pathogenic	-0.658	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
K/G	0.9647	likely_pathogenic	0.9524	pathogenic	-1.954	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
K/H	0.6799	likely_pathogenic	0.6401	pathogenic	-1.802	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
K/I	0.9029	likely_pathogenic	0.8836	pathogenic	-0.077	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
K/L	0.8564	likely_pathogenic	0.8331	pathogenic	-0.077	Destabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
K/M	0.6349	likely_pathogenic	0.6066	pathogenic	-0.546	Destabilizing	1.0	D	0.815	deleterious	N	0.502165342	None	None	N
K/N	0.9735	likely_pathogenic	0.9636	pathogenic	-2.192	Highly Destabilizing	0.993	D	0.799	deleterious	N	0.513021798	None	None	N
K/P	0.9994	likely_pathogenic	0.9989	pathogenic	-0.526	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
K/Q	0.4513	ambiguous	0.4045	ambiguous	-1.711	Destabilizing	0.993	D	0.799	deleterious	N	0.472204932	None	None	N
K/R	0.096	likely_benign	0.0952	benign	-1.218	Destabilizing	0.235	N	0.377	neutral	N	0.445349267	None	None	N
K/S	0.9571	likely_pathogenic	0.9429	pathogenic	-2.567	Highly Destabilizing	0.983	D	0.696	prob.neutral	None	None	None	None	N
K/T	0.8639	likely_pathogenic	0.827	pathogenic	-1.984	Destabilizing	0.997	D	0.787	deleterious	N	0.500398045	None	None	N
K/V	0.8438	likely_pathogenic	0.8175	pathogenic	-0.526	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
K/W	0.9432	likely_pathogenic	0.9287	pathogenic	-0.845	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/Y	0.8887	likely_pathogenic	0.8703	pathogenic	-0.482	Destabilizing	0.999	D	0.855	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.