TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30486	91681;91682;91683	chr2:178551075;178551074;178551073	chr2:179415802;179415801;179415800
N2AB	28845	86758;86759;86760	chr2:178551075;178551074;178551073	chr2:179415802;179415801;179415800
N2A	27918	83977;83978;83979	chr2:178551075;178551074;178551073	chr2:179415802;179415801;179415800
N2B	21421	64486;64487;64488	chr2:178551075;178551074;178551073	chr2:179415802;179415801;179415800
Novex-1	21546	64861;64862;64863	chr2:178551075;178551074;178551073	chr2:179415802;179415801;179415800
Novex-2	21613	65062;65063;65064	chr2:178551075;178551074;178551073	chr2:179415802;179415801;179415800
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: Fn3-110
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.0985
• 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/H	None	None	1.0	D	0.797	0.863	0.953830594898	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85958E-06	0	0
L/V	None	None	0.999	D	0.843	0.696	0.844428606866	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9548	likely_pathogenic	0.9696	pathogenic	-2.509	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/C	0.8997	likely_pathogenic	0.9302	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9995	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/E	0.9956	likely_pathogenic	0.9972	pathogenic	-1.955	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/F	0.751	likely_pathogenic	0.8287	pathogenic	-1.737	Destabilizing	1.0	D	0.856	deleterious	D	0.634330508	None	None	N
L/G	0.991	likely_pathogenic	0.9942	pathogenic	-2.981	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/H	0.9848	likely_pathogenic	0.9909	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.797	deleterious	D	0.667176447	None	None	N
L/I	0.338	likely_benign	0.3865	ambiguous	-1.193	Destabilizing	0.999	D	0.832	deleterious	D	0.620320266	None	None	N
L/K	0.9906	likely_pathogenic	0.9938	pathogenic	-1.757	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/M	0.431	ambiguous	0.5072	ambiguous	-1.122	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/N	0.9897	likely_pathogenic	0.9931	pathogenic	-1.85	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/P	0.9936	likely_pathogenic	0.9962	pathogenic	-1.607	Destabilizing	1.0	D	0.842	deleterious	D	0.667176447	None	None	N
L/Q	0.977	likely_pathogenic	0.9864	pathogenic	-1.88	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/R	0.9811	likely_pathogenic	0.9882	pathogenic	-1.275	Destabilizing	1.0	D	0.829	deleterious	D	0.651157086	None	None	N
L/S	0.992	likely_pathogenic	0.9956	pathogenic	-2.671	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/T	0.9641	likely_pathogenic	0.9751	pathogenic	-2.391	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/V	0.4524	ambiguous	0.52	ambiguous	-1.607	Destabilizing	0.999	D	0.843	deleterious	D	0.583748974	None	None	N
L/W	0.9799	likely_pathogenic	0.9897	pathogenic	-1.88	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/Y	0.9737	likely_pathogenic	0.9846	pathogenic	-1.655	Destabilizing	1.0	D	0.815	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.