TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6924	20995;20996;20997	chr2:178725434;178725433;178725432	chr2:179590161;179590160;179590159
N2AB	6607	20044;20045;20046	chr2:178725434;178725433;178725432	chr2:179590161;179590160;179590159
N2A	5680	17263;17264;17265	chr2:178725434;178725433;178725432	chr2:179590161;179590160;179590159
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-53
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.5968
• 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	rs369993514	None	0.999	D	0.697	0.33	0.17258766438	gnomAD-4.0.0	6.8523E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00335E-07	0	0
K/T	None	None	0.999	N	0.745	0.49	0.52463718601	gnomAD-4.0.0	5.48061E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.20134E-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	0.6276	likely_pathogenic	0.6618	pathogenic	-0.683	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
K/C	0.8574	likely_pathogenic	0.8592	pathogenic	-0.588	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.7601	likely_pathogenic	0.7751	pathogenic	-0.432	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/E	0.3391	likely_benign	0.3917	ambiguous	-0.288	Destabilizing	0.996	D	0.611	neutral	D	0.522765193	None	None	N
K/F	0.8615	likely_pathogenic	0.8697	pathogenic	-0.154	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/G	0.7351	likely_pathogenic	0.7395	pathogenic	-1.101	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.4189	ambiguous	0.4208	ambiguous	-1.465	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/I	0.4522	ambiguous	0.4937	ambiguous	0.427	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.5372	ambiguous	0.5703	pathogenic	0.427	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.3582	ambiguous	0.4042	ambiguous	0.334	Stabilizing	1.0	D	0.738	prob.delet.	N	0.498978554	None	None	N
K/N	0.5305	ambiguous	0.5457	ambiguous	-0.729	Destabilizing	0.999	D	0.697	prob.neutral	D	0.537446644	None	None	N
K/P	0.8651	likely_pathogenic	0.8689	pathogenic	0.087	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/Q	0.2105	likely_benign	0.228	benign	-0.711	Destabilizing	0.999	D	0.693	prob.neutral	N	0.488708204	None	None	N
K/R	0.0925	likely_benign	0.0916	benign	-0.893	Destabilizing	0.64	D	0.336	neutral	N	0.495792022	None	None	N
K/S	0.6316	likely_pathogenic	0.6496	pathogenic	-1.338	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
K/T	0.2999	likely_benign	0.337	benign	-0.974	Destabilizing	0.999	D	0.745	deleterious	N	0.519591602	None	None	N
K/V	0.4754	ambiguous	0.5097	ambiguous	0.087	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/W	0.8331	likely_pathogenic	0.8343	pathogenic	-0.065	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.7018	likely_pathogenic	0.7116	pathogenic	0.203	Stabilizing	1.0	D	0.733	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.