TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17267	52024;52025;52026	chr2:178609511;178609510;178609509	chr2:179474238;179474237;179474236
N2AB	15626	47101;47102;47103	chr2:178609511;178609510;178609509	chr2:179474238;179474237;179474236
N2A	14699	44320;44321;44322	chr2:178609511;178609510;178609509	chr2:179474238;179474237;179474236
N2B	8202	24829;24830;24831	chr2:178609511;178609510;178609509	chr2:179474238;179474237;179474236
Novex-1	8327	25204;25205;25206	chr2:178609511;178609510;178609509	chr2:179474238;179474237;179474236
Novex-2	8394	25405;25406;25407	chr2:178609511;178609510;178609509	chr2:179474238;179474237;179474236
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-112
• Domain position: 17
• Structural Position: 30
• Q(SASA): 0.0976
• 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	rs758364988	-1.678	1.0	D	0.803	0.342	0.606442066225	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.71E-05	None	0	0	None	0	None	0	0	0
L/F	rs758364988	-1.678	1.0	D	0.803	0.342	0.606442066225	gnomAD-4.0.0	4.78184E-06	None	None	None	None	N	None	0	6.86405E-05	None	0	0	None	0	0	0	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	0.909	likely_pathogenic	0.9024	pathogenic	-2.747	Highly Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/C	0.8968	likely_pathogenic	0.8985	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9989	pathogenic	-3.631	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/E	0.993	likely_pathogenic	0.9916	pathogenic	-3.32	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/F	0.5349	ambiguous	0.5009	ambiguous	-1.697	Destabilizing	1.0	D	0.803	deleterious	D	0.533347546	None	None	N
L/G	0.9905	likely_pathogenic	0.9895	pathogenic	-3.342	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/H	0.9877	likely_pathogenic	0.9864	pathogenic	-2.982	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.597575309	None	None	N
L/I	0.1067	likely_benign	0.1022	benign	-0.964	Destabilizing	0.999	D	0.559	neutral	D	0.550230871	None	None	N
L/K	0.9884	likely_pathogenic	0.9867	pathogenic	-2.34	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/M	0.265	likely_benign	0.259	benign	-1.026	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/N	0.9953	likely_pathogenic	0.9948	pathogenic	-3.015	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
L/P	0.9918	likely_pathogenic	0.9904	pathogenic	-1.548	Destabilizing	1.0	D	0.911	deleterious	D	0.597575309	None	None	N
L/Q	0.9814	likely_pathogenic	0.9793	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/R	0.9814	likely_pathogenic	0.9789	pathogenic	-2.287	Highly Destabilizing	1.0	D	0.898	deleterious	D	0.597575309	None	None	N
L/S	0.99	likely_pathogenic	0.9893	pathogenic	-3.58	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/T	0.938	likely_pathogenic	0.9355	pathogenic	-3.107	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/V	0.1527	likely_benign	0.1433	benign	-1.548	Destabilizing	0.999	D	0.581	neutral	D	0.545490064	None	None	N
L/W	0.9402	likely_pathogenic	0.9327	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/Y	0.9644	likely_pathogenic	0.9602	pathogenic	-1.876	Destabilizing	1.0	D	0.851	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.