TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35143	105652;105653;105654	chr2:178531188;178531187;178531186	chr2:179395915;179395914;179395913
N2AB	33502	100729;100730;100731	chr2:178531188;178531187;178531186	chr2:179395915;179395914;179395913
N2A	32575	97948;97949;97950	chr2:178531188;178531187;178531186	chr2:179395915;179395914;179395913
N2B	26078	78457;78458;78459	chr2:178531188;178531187;178531186	chr2:179395915;179395914;179395913
Novex-1	26203	78832;78833;78834	chr2:178531188;178531187;178531186	chr2:179395915;179395914;179395913
Novex-2	26270	79033;79034;79035	chr2:178531188;178531187;178531186	chr2:179395915;179395914;179395913
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-164
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2588
• 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
G/S	rs1441874026	None	1.0	D	0.857	0.891	0.620928753958	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/S	rs1441874026	None	1.0	D	0.857	0.891	0.620928753958	gnomAD-4.0.0	6.57194E-06	None	None	None	None	N	None	2.41371E-05	0	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
G/A	0.5165	ambiguous	0.6266	pathogenic	-0.481	Destabilizing	1.0	D	0.787	deleterious	D	0.585750964	None	None	N
G/C	0.7741	likely_pathogenic	0.8311	pathogenic	-1.014	Destabilizing	1.0	D	0.858	deleterious	D	0.659023913	None	None	N
G/D	0.3649	ambiguous	0.431	ambiguous	-0.711	Destabilizing	1.0	D	0.886	deleterious	D	0.58413653	None	None	N
G/E	0.4604	ambiguous	0.5659	pathogenic	-0.867	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
G/F	0.9425	likely_pathogenic	0.9653	pathogenic	-1.164	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/H	0.7926	likely_pathogenic	0.8372	pathogenic	-0.681	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/I	0.9267	likely_pathogenic	0.9666	pathogenic	-0.571	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/K	0.7128	likely_pathogenic	0.7944	pathogenic	-0.881	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
G/L	0.9005	likely_pathogenic	0.9376	pathogenic	-0.571	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
G/M	0.8966	likely_pathogenic	0.9322	pathogenic	-0.497	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/N	0.4596	ambiguous	0.5052	ambiguous	-0.589	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/P	0.9927	likely_pathogenic	0.9965	pathogenic	-0.508	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
G/Q	0.6826	likely_pathogenic	0.7506	pathogenic	-0.906	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
G/R	0.6392	likely_pathogenic	0.7296	pathogenic	-0.42	Destabilizing	1.0	D	0.887	deleterious	D	0.613580362	None	None	N
G/S	0.2684	likely_benign	0.3229	benign	-0.769	Destabilizing	1.0	D	0.857	deleterious	D	0.591121112	None	None	N
G/T	0.6021	likely_pathogenic	0.7055	pathogenic	-0.856	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/V	0.8432	likely_pathogenic	0.9161	pathogenic	-0.508	Destabilizing	1.0	D	0.854	deleterious	D	0.658822109	None	None	N
G/W	0.8098	likely_pathogenic	0.8737	pathogenic	-1.283	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/Y	0.8581	likely_pathogenic	0.8995	pathogenic	-0.942	Destabilizing	1.0	D	0.864	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.