TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20044	60355;60356;60357	chr2:178591689;178591688;178591687	chr2:179456416;179456415;179456414
N2AB	18403	55432;55433;55434	chr2:178591689;178591688;178591687	chr2:179456416;179456415;179456414
N2A	17476	52651;52652;52653	chr2:178591689;178591688;178591687	chr2:179456416;179456415;179456414
N2B	10979	33160;33161;33162	chr2:178591689;178591688;178591687	chr2:179456416;179456415;179456414
Novex-1	11104	33535;33536;33537	chr2:178591689;178591688;178591687	chr2:179456416;179456415;179456414
Novex-2	11171	33736;33737;33738	chr2:178591689;178591688;178591687	chr2:179456416;179456415;179456414
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: Fn3-33
• Domain position: 68
• Structural Position: 102
• Q(SASA): 0.3617
• 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	rs1223532991	-0.229	0.999	N	0.527	0.382	0.258779203287	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/E	rs1223532991	-0.229	0.999	N	0.527	0.382	0.258779203287	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85961E-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	0.4754	ambiguous	0.4538	ambiguous	-0.718	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	N
K/C	0.6627	likely_pathogenic	0.678	pathogenic	-0.513	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.7283	likely_pathogenic	0.7268	pathogenic	-0.466	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/E	0.2593	likely_benign	0.2533	benign	-0.336	Destabilizing	0.999	D	0.527	neutral	N	0.443559756	None	None	N
K/F	0.8314	likely_pathogenic	0.8245	pathogenic	-0.234	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/G	0.5801	likely_pathogenic	0.5698	pathogenic	-1.116	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/H	0.3122	likely_benign	0.3189	benign	-1.458	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/I	0.5076	ambiguous	0.4678	ambiguous	0.335	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/L	0.4797	ambiguous	0.4802	ambiguous	0.335	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/M	0.2637	likely_benign	0.2628	benign	0.251	Stabilizing	1.0	D	0.647	neutral	N	0.483771582	None	None	N
K/N	0.4347	ambiguous	0.4252	ambiguous	-0.665	Destabilizing	1.0	D	0.659	neutral	N	0.465263179	None	None	N
K/P	0.9818	likely_pathogenic	0.9836	pathogenic	0.014	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/Q	0.14	likely_benign	0.1359	benign	-0.669	Destabilizing	1.0	D	0.639	neutral	N	0.466263257	None	None	N
K/R	0.0937	likely_benign	0.095	benign	-0.823	Destabilizing	0.999	D	0.536	neutral	N	0.465953826	None	None	N
K/S	0.4939	ambiguous	0.4646	ambiguous	-1.241	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
K/T	0.264	likely_benign	0.2444	benign	-0.9	Destabilizing	1.0	D	0.66	neutral	N	0.408420101	None	None	N
K/V	0.4201	ambiguous	0.3904	ambiguous	0.014	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/W	0.8647	likely_pathogenic	0.8647	pathogenic	-0.142	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/Y	0.7112	likely_pathogenic	0.7186	pathogenic	0.104	Stabilizing	1.0	D	0.677	prob.neutral	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.