TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16625	50098;50099;50100	chr2:178612848;178612847;178612846	chr2:179477575;179477574;179477573
N2AB	14984	45175;45176;45177	chr2:178612848;178612847;178612846	chr2:179477575;179477574;179477573
N2A	14057	42394;42395;42396	chr2:178612848;178612847;178612846	chr2:179477575;179477574;179477573
N2B	7560	22903;22904;22905	chr2:178612848;178612847;178612846	chr2:179477575;179477574;179477573
Novex-1	7685	23278;23279;23280	chr2:178612848;178612847;178612846	chr2:179477575;179477574;179477573
Novex-2	7752	23479;23480;23481	chr2:178612848;178612847;178612846	chr2:179477575;179477574;179477573
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-8
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0896
• 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/G	None	None	1.0	D	0.891	0.903	0.90093157036	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9071	likely_pathogenic	0.9229	pathogenic	-2.627	Highly Destabilizing	0.998	D	0.678	prob.neutral	D	0.74535921	None	None	N
V/C	0.9641	likely_pathogenic	0.9672	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.9993	pathogenic	-3.429	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.816292727	None	None	N
V/E	0.9941	likely_pathogenic	0.9968	pathogenic	-3.132	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/F	0.9216	likely_pathogenic	0.9441	pathogenic	-1.323	Destabilizing	0.999	D	0.842	deleterious	D	0.815248958	None	None	N
V/G	0.9416	likely_pathogenic	0.9637	pathogenic	-3.181	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.816292727	None	None	N
V/H	0.9987	likely_pathogenic	0.9993	pathogenic	-2.896	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1132	likely_benign	0.104	benign	-1.003	Destabilizing	0.767	D	0.333	neutral	N	0.52180713	None	None	N
V/K	0.9961	likely_pathogenic	0.998	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.7347	likely_pathogenic	0.7572	pathogenic	-1.003	Destabilizing	0.981	D	0.625	neutral	D	0.634028452	None	None	N
V/M	0.8305	likely_pathogenic	0.8581	pathogenic	-1.409	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/N	0.9939	likely_pathogenic	0.9966	pathogenic	-2.641	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/P	0.9944	likely_pathogenic	0.9966	pathogenic	-1.529	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/Q	0.9939	likely_pathogenic	0.9964	pathogenic	-2.305	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/R	0.9917	likely_pathogenic	0.9957	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
V/S	0.9724	likely_pathogenic	0.9822	pathogenic	-3.129	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/T	0.9376	likely_pathogenic	0.9516	pathogenic	-2.693	Highly Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9993	pathogenic	-1.843	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Y	0.9939	likely_pathogenic	0.9962	pathogenic	-1.649	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.