TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9576	28951;28952;28953	chr2:178709593;178709592;178709591	chr2:179574320;179574319;179574318
N2AB	9259	28000;28001;28002	chr2:178709593;178709592;178709591	chr2:179574320;179574319;179574318
N2A	8332	25219;25220;25221	chr2:178709593;178709592;178709591	chr2:179574320;179574319;179574318
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-81
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.4544
• 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/P	None	None	0.988	None	0.58	0.401	0.846142072032	gnomAD-4.0.0	6.84753E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00255E-07	0	0
L/V	rs780753483	-0.283	0.826	None	0.433	0.069	0.48512917806	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.7E-05	None	0	0	None	0	None	0	0	0
L/V	rs780753483	-0.283	0.826	None	0.433	0.069	0.48512917806	gnomAD-4.0.0	4.77628E-06	None	None	None	None	N	None	0	6.86028E-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	0.3832	ambiguous	0.3706	ambiguous	-1.158	Destabilizing	0.17	N	0.298	neutral	None	None	None	None	N
L/C	0.7435	likely_pathogenic	0.7354	pathogenic	-0.753	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	N
L/D	0.8533	likely_pathogenic	0.8624	pathogenic	-0.292	Destabilizing	0.982	D	0.572	neutral	None	None	None	None	N
L/E	0.5686	likely_pathogenic	0.5621	ambiguous	-0.309	Destabilizing	0.939	D	0.561	neutral	None	None	None	None	N
L/F	0.1965	likely_benign	0.1852	benign	-0.788	Destabilizing	0.046	N	0.345	neutral	None	None	None	None	N
L/G	0.7635	likely_pathogenic	0.7615	pathogenic	-1.435	Destabilizing	0.939	D	0.503	neutral	None	None	None	None	N
L/H	0.4095	ambiguous	0.4217	ambiguous	-0.548	Destabilizing	0.999	D	0.562	neutral	None	None	None	None	N
L/I	0.124	likely_benign	0.1167	benign	-0.499	Destabilizing	0.939	D	0.433	neutral	None	None	None	None	N
L/K	0.5629	ambiguous	0.5725	pathogenic	-0.643	Destabilizing	0.939	D	0.535	neutral	None	None	None	None	N
L/M	0.1677	likely_benign	0.1533	benign	-0.486	Destabilizing	0.996	D	0.499	neutral	None	None	None	None	N
L/N	0.563	ambiguous	0.5599	ambiguous	-0.483	Destabilizing	0.982	D	0.581	neutral	None	None	None	None	N
L/P	0.8589	likely_pathogenic	0.8949	pathogenic	-0.686	Destabilizing	0.988	D	0.58	neutral	None	None	None	None	N
L/Q	0.3087	likely_benign	0.2989	benign	-0.628	Destabilizing	0.988	D	0.579	neutral	None	None	None	None	N
L/R	0.4465	ambiguous	0.4575	ambiguous	-0.107	Destabilizing	0.988	D	0.585	neutral	None	None	None	None	N
L/S	0.3435	ambiguous	0.3253	benign	-1.092	Destabilizing	0.2	N	0.422	neutral	None	None	None	None	N
L/T	0.2987	likely_benign	0.2856	benign	-0.983	Destabilizing	0.884	D	0.452	neutral	None	None	None	None	N
L/V	0.1266	likely_benign	0.114	benign	-0.686	Destabilizing	0.826	D	0.433	neutral	None	None	None	None	N
L/W	0.4568	ambiguous	0.4727	ambiguous	-0.82	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
L/Y	0.5085	ambiguous	0.527	ambiguous	-0.586	Destabilizing	0.964	D	0.565	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.