TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18821	56686;56687;56688	chr2:178599332;178599331;178599330	chr2:179464059;179464058;179464057
N2AB	17180	51763;51764;51765	chr2:178599332;178599331;178599330	chr2:179464059;179464058;179464057
N2A	16253	48982;48983;48984	chr2:178599332;178599331;178599330	chr2:179464059;179464058;179464057
N2B	9756	29491;29492;29493	chr2:178599332;178599331;178599330	chr2:179464059;179464058;179464057
Novex-1	9881	29866;29867;29868	chr2:178599332;178599331;178599330	chr2:179464059;179464058;179464057
Novex-2	9948	30067;30068;30069	chr2:178599332;178599331;178599330	chr2:179464059;179464058;179464057
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-24
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1255
• 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/I	rs1576247575	None	0.997	N	0.655	0.263	0.529260826313	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1576247575	None	0.997	N	0.655	0.263	0.529260826313	gnomAD-4.0.0	1.17994E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52738E-05	1.10676E-05	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	0.4514	ambiguous	0.3902	ambiguous	-2.307	Highly Destabilizing	0.999	D	0.687	prob.neutral	N	0.519172235	None	None	N
V/C	0.7652	likely_pathogenic	0.7197	pathogenic	-1.967	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
V/D	0.7174	likely_pathogenic	0.6283	pathogenic	-3.37	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/E	0.5366	ambiguous	0.4544	ambiguous	-3.193	Highly Destabilizing	1.0	D	0.755	deleterious	N	0.501314406	None	None	N
V/F	0.3208	likely_benign	0.2703	benign	-1.32	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/G	0.6007	likely_pathogenic	0.5059	ambiguous	-2.761	Highly Destabilizing	1.0	D	0.773	deleterious	N	0.503627275	None	None	N
V/H	0.7175	likely_pathogenic	0.6493	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/I	0.0721	likely_benign	0.0731	benign	-1.035	Destabilizing	0.997	D	0.655	neutral	N	0.423800559	None	None	N
V/K	0.5442	ambiguous	0.4614	ambiguous	-2.024	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/L	0.3028	likely_benign	0.2617	benign	-1.035	Destabilizing	0.997	D	0.67	neutral	N	0.487214532	None	None	N
V/M	0.2053	likely_benign	0.1795	benign	-1.126	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
V/N	0.5465	ambiguous	0.453	ambiguous	-2.343	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/P	0.9911	likely_pathogenic	0.9872	pathogenic	-1.437	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/Q	0.5173	ambiguous	0.4506	ambiguous	-2.233	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/R	0.4845	ambiguous	0.4058	ambiguous	-1.709	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/S	0.4659	ambiguous	0.3937	ambiguous	-2.811	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/T	0.2625	likely_benign	0.2447	benign	-2.527	Highly Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
V/W	0.8974	likely_pathogenic	0.8734	pathogenic	-1.901	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/Y	0.6899	likely_pathogenic	0.621	pathogenic	-1.632	Destabilizing	1.0	D	0.785	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.