TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4928	15007;15008;15009	chr2:178735664;178735663;178735662	chr2:179600391;179600390;179600389
N2AB	4611	14056;14057;14058	chr2:178735664;178735663;178735662	chr2:179600391;179600390;179600389
N2A	3684	11275;11276;11277	chr2:178735664;178735663;178735662	chr2:179600391;179600390;179600389
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-32
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1444
• 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/F	rs758924238	-1.664	0.627	D	0.628	0.356	0.536051623013	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/F	rs758924238	-1.664	0.627	D	0.628	0.356	0.536051623013	gnomAD-4.0.0	3.42118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49727E-06	0	0
L/R	rs1347273297	None	0.627	D	0.678	0.58	0.823228597577	gnomAD-4.0.0	3.18286E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	2.85817E-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	0.4747	ambiguous	0.5103	ambiguous	-2.344	Highly Destabilizing	0.116	N	0.582	neutral	None	None	None	None	N
L/C	0.5987	likely_pathogenic	0.6345	pathogenic	-1.616	Destabilizing	0.944	D	0.625	neutral	None	None	None	None	N
L/D	0.9266	likely_pathogenic	0.9468	pathogenic	-2.092	Highly Destabilizing	0.69	D	0.698	prob.neutral	None	None	None	None	N
L/E	0.7585	likely_pathogenic	0.8044	pathogenic	-1.885	Destabilizing	0.527	D	0.694	prob.neutral	None	None	None	None	N
L/F	0.172	likely_benign	0.1954	benign	-1.4	Destabilizing	0.627	D	0.628	neutral	D	0.607983544	None	None	N
L/G	0.769	likely_pathogenic	0.8065	pathogenic	-2.849	Highly Destabilizing	0.241	N	0.681	prob.neutral	None	None	None	None	N
L/H	0.4879	ambiguous	0.5381	ambiguous	-2.011	Highly Destabilizing	0.928	D	0.667	neutral	D	0.752706044	None	None	N
L/I	0.0682	likely_benign	0.0716	benign	-0.903	Destabilizing	0.001	N	0.175	neutral	N	0.469810259	None	None	N
L/K	0.6337	likely_pathogenic	0.6872	pathogenic	-1.749	Destabilizing	0.527	D	0.669	neutral	None	None	None	None	N
L/M	0.1341	likely_benign	0.1425	benign	-0.848	Destabilizing	0.69	D	0.639	neutral	None	None	None	None	N
L/N	0.6657	likely_pathogenic	0.7209	pathogenic	-2.008	Highly Destabilizing	0.527	D	0.714	prob.delet.	None	None	None	None	N
L/P	0.6612	likely_pathogenic	0.7163	pathogenic	-1.362	Destabilizing	0.627	D	0.712	prob.delet.	D	0.65436035	None	None	N
L/Q	0.4573	ambiguous	0.4904	ambiguous	-1.883	Destabilizing	0.69	D	0.667	neutral	None	None	None	None	N
L/R	0.5143	ambiguous	0.5626	ambiguous	-1.477	Destabilizing	0.627	D	0.678	prob.neutral	D	0.676680096	None	None	N
L/S	0.62	likely_pathogenic	0.6661	pathogenic	-2.747	Highly Destabilizing	0.005	N	0.516	neutral	None	None	None	None	N
L/T	0.4444	ambiguous	0.4781	ambiguous	-2.381	Highly Destabilizing	0.241	N	0.582	neutral	None	None	None	None	N
L/V	0.0984	likely_benign	0.1022	benign	-1.362	Destabilizing	0.003	N	0.183	neutral	N	0.516502007	None	None	N
L/W	0.4136	ambiguous	0.4529	ambiguous	-1.6	Destabilizing	0.981	D	0.654	neutral	None	None	None	None	N
L/Y	0.4341	ambiguous	0.4888	ambiguous	-1.344	Destabilizing	0.818	D	0.695	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.