TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17442	52549;52550;52551	chr2:178608687;178608686;178608685	chr2:179473414;179473413;179473412
N2AB	15801	47626;47627;47628	chr2:178608687;178608686;178608685	chr2:179473414;179473413;179473412
N2A	14874	44845;44846;44847	chr2:178608687;178608686;178608685	chr2:179473414;179473413;179473412
N2B	8377	25354;25355;25356	chr2:178608687;178608686;178608685	chr2:179473414;179473413;179473412
Novex-1	8502	25729;25730;25731	chr2:178608687;178608686;178608685	chr2:179473414;179473413;179473412
Novex-2	8569	25930;25931;25932	chr2:178608687;178608686;178608685	chr2:179473414;179473413;179473412
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-14
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.1165
• 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
L/V	rs2055526499	None	0.003	N	0.385	0.067	0.514240282655	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
L/V	rs2055526499	None	0.003	N	0.385	0.067	0.514240282655	gnomAD-4.0.0	6.20279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.09885E-04	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
L/A	0.2584	likely_benign	0.2762	benign	-2.788	Highly Destabilizing	0.404	N	0.666	neutral	None	None	None	None	N
L/C	0.3447	ambiguous	0.3524	ambiguous	-1.688	Destabilizing	0.973	D	0.701	prob.neutral	None	None	None	None	N
L/D	0.7162	likely_pathogenic	0.7415	pathogenic	-3.29	Highly Destabilizing	0.906	D	0.785	deleterious	None	None	None	None	N
L/E	0.2882	likely_benign	0.3043	benign	-3.006	Highly Destabilizing	0.906	D	0.756	deleterious	None	None	None	None	N
L/F	0.1579	likely_benign	0.1601	benign	-1.638	Destabilizing	0.782	D	0.62	neutral	N	0.448850932	None	None	N
L/G	0.6385	likely_pathogenic	0.6719	pathogenic	-3.343	Highly Destabilizing	0.906	D	0.749	deleterious	None	None	None	None	N
L/H	0.265	likely_benign	0.2459	benign	-2.929	Highly Destabilizing	0.988	D	0.787	deleterious	N	0.448504215	None	None	N
L/I	0.0692	likely_benign	0.0685	benign	-1.126	Destabilizing	0.001	N	0.321	neutral	N	0.376316043	None	None	N
L/K	0.4522	ambiguous	0.44	ambiguous	-2.012	Highly Destabilizing	0.906	D	0.713	prob.delet.	None	None	None	None	N
L/M	0.1008	likely_benign	0.1007	benign	-1.116	Destabilizing	0.826	D	0.676	prob.neutral	None	None	None	None	N
L/N	0.4333	ambiguous	0.4437	ambiguous	-2.555	Highly Destabilizing	0.967	D	0.797	deleterious	None	None	None	None	N
L/P	0.9749	likely_pathogenic	0.9783	pathogenic	-1.67	Destabilizing	0.957	D	0.789	deleterious	N	0.472761136	None	None	N
L/Q	0.1723	likely_benign	0.1631	benign	-2.289	Highly Destabilizing	0.967	D	0.753	deleterious	None	None	None	None	N
L/R	0.3416	ambiguous	0.3266	benign	-1.912	Destabilizing	0.879	D	0.745	deleterious	N	0.430398457	None	None	N
L/S	0.2685	likely_benign	0.2879	benign	-3.122	Highly Destabilizing	0.826	D	0.683	prob.neutral	None	None	None	None	N
L/T	0.1562	likely_benign	0.1641	benign	-2.699	Highly Destabilizing	0.575	D	0.663	neutral	None	None	None	None	N
L/V	0.0711	likely_benign	0.0728	benign	-1.67	Destabilizing	0.003	N	0.385	neutral	N	0.417834592	None	None	N
L/W	0.3582	ambiguous	0.3357	benign	-2.079	Highly Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	N
L/Y	0.3452	ambiguous	0.3451	ambiguous	-1.851	Destabilizing	0.906	D	0.723	prob.delet.	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.