TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14181	42766;42767;42768	chr2:178633958;178633957;178633956	chr2:179498685;179498684;179498683
N2AB	12540	37843;37844;37845	chr2:178633958;178633957;178633956	chr2:179498685;179498684;179498683
N2A	11613	35062;35063;35064	chr2:178633958;178633957;178633956	chr2:179498685;179498684;179498683
N2B	5116	15571;15572;15573	chr2:178633958;178633957;178633956	chr2:179498685;179498684;179498683
Novex-1	5241	15946;15947;15948	chr2:178633958;178633957;178633956	chr2:179498685;179498684;179498683
Novex-2	5308	16147;16148;16149	chr2:178633958;178633957;178633956	chr2:179498685;179498684;179498683
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: Ig-92
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.2602
• 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	None	None	0.981	N	0.49	0.342	0.603196339416	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85974E-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	0.8992	likely_pathogenic	0.9056	pathogenic	-2.42	Highly Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
L/C	0.9009	likely_pathogenic	0.9016	pathogenic	-1.421	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/D	0.996	likely_pathogenic	0.9975	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/E	0.96	likely_pathogenic	0.9752	pathogenic	-2.498	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/F	0.4968	ambiguous	0.4969	ambiguous	-1.566	Destabilizing	0.999	D	0.734	prob.delet.	D	0.677128754	None	None	N
L/G	0.98	likely_pathogenic	0.9843	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/H	0.927	likely_pathogenic	0.9419	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.678762675	None	None	N
L/I	0.1018	likely_benign	0.0947	benign	-1.06	Destabilizing	0.767	D	0.277	neutral	N	0.469403573	None	None	N
L/K	0.9275	likely_pathogenic	0.9572	pathogenic	-1.877	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/M	0.2665	likely_benign	0.2571	benign	-0.788	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/N	0.9737	likely_pathogenic	0.9801	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/P	0.977	likely_pathogenic	0.9855	pathogenic	-1.495	Destabilizing	1.0	D	0.857	deleterious	D	0.639439359	None	None	N
L/Q	0.8646	likely_pathogenic	0.9067	pathogenic	-2.095	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/R	0.8999	likely_pathogenic	0.935	pathogenic	-1.481	Destabilizing	1.0	D	0.851	deleterious	D	0.678330461	None	None	N
L/S	0.9706	likely_pathogenic	0.9735	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/T	0.8902	likely_pathogenic	0.8975	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/V	0.176	likely_benign	0.1621	benign	-1.495	Destabilizing	0.981	D	0.49	neutral	N	0.510554556	None	None	N
L/W	0.7958	likely_pathogenic	0.8213	pathogenic	-1.874	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/Y	0.8643	likely_pathogenic	0.8719	pathogenic	-1.574	Destabilizing	1.0	D	0.837	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.