TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29299	88120;88121;88122	chr2:178557367;178557366;178557365	chr2:179422094;179422093;179422092
N2AB	27658	83197;83198;83199	chr2:178557367;178557366;178557365	chr2:179422094;179422093;179422092
N2A	26731	80416;80417;80418	chr2:178557367;178557366;178557365	chr2:179422094;179422093;179422092
N2B	20234	60925;60926;60927	chr2:178557367;178557366;178557365	chr2:179422094;179422093;179422092
Novex-1	20359	61300;61301;61302	chr2:178557367;178557366;178557365	chr2:179422094;179422093;179422092
Novex-2	20426	61501;61502;61503	chr2:178557367;178557366;178557365	chr2:179422094;179422093;179422092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-101
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1271
• 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
V/A	rs1001499509	None	0.998	N	0.619	0.405	0.626601018324	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85771E-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
V/A	0.4684	ambiguous	0.4437	ambiguous	-1.786	Destabilizing	0.998	D	0.619	neutral	N	0.490569843	None	None	N
V/C	0.8778	likely_pathogenic	0.8671	pathogenic	-1.411	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/D	0.9601	likely_pathogenic	0.9643	pathogenic	-1.868	Destabilizing	1.0	D	0.832	deleterious	N	0.482607548	None	None	N
V/E	0.9322	likely_pathogenic	0.9286	pathogenic	-1.634	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/F	0.6696	likely_pathogenic	0.6387	pathogenic	-0.983	Destabilizing	0.999	D	0.792	deleterious	N	0.487959465	None	None	N
V/G	0.7241	likely_pathogenic	0.7367	pathogenic	-2.352	Highly Destabilizing	1.0	D	0.842	deleterious	D	0.527970317	None	None	N
V/H	0.9747	likely_pathogenic	0.9756	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.1127	likely_benign	0.102	benign	-0.214	Destabilizing	0.767	D	0.26	neutral	N	0.480368705	None	None	N
V/K	0.9554	likely_pathogenic	0.9596	pathogenic	-1.389	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/L	0.5083	ambiguous	0.4573	ambiguous	-0.214	Destabilizing	0.981	D	0.619	neutral	N	0.501682552	None	None	N
V/M	0.4263	ambiguous	0.3802	ambiguous	-0.35	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/N	0.8876	likely_pathogenic	0.8862	pathogenic	-1.694	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/P	0.9662	likely_pathogenic	0.9734	pathogenic	-0.709	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Q	0.9337	likely_pathogenic	0.9351	pathogenic	-1.478	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/R	0.9477	likely_pathogenic	0.9545	pathogenic	-1.372	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/S	0.7497	likely_pathogenic	0.7498	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/T	0.6202	likely_pathogenic	0.6076	pathogenic	-2.011	Highly Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
V/W	0.9891	likely_pathogenic	0.989	pathogenic	-1.43	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9329	likely_pathogenic	0.9295	pathogenic	-1.016	Destabilizing	1.0	D	0.791	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.