TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24625	74098;74099;74100	chr2:178572259;178572258;178572257	chr2:179436986;179436985;179436984
N2AB	22984	69175;69176;69177	chr2:178572259;178572258;178572257	chr2:179436986;179436985;179436984
N2A	22057	66394;66395;66396	chr2:178572259;178572258;178572257	chr2:179436986;179436985;179436984
N2B	15560	46903;46904;46905	chr2:178572259;178572258;178572257	chr2:179436986;179436985;179436984
Novex-1	15685	47278;47279;47280	chr2:178572259;178572258;178572257	chr2:179436986;179436985;179436984
Novex-2	15752	47479;47480;47481	chr2:178572259;178572258;178572257	chr2:179436986;179436985;179436984
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-67
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2707
• 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/M	rs545556079	-0.827	0.995	N	0.771	0.261	0.570999777189	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/M	rs545556079	-0.827	0.995	N	0.771	0.261	0.570999777189	gnomAD-4.0.0	1.36886E-06	None	None	None	None	N	None	0	4.47427E-05	None	0	0	None	0	0	0	0	0
L/V	None	None	0.102	N	0.383	0.042	0.218845423259	gnomAD-4.0.0	6.84428E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16007E-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
L/A	0.7451	likely_pathogenic	0.6872	pathogenic	-2.039	Highly Destabilizing	0.997	D	0.667	neutral	None	None	None	None	N
L/C	0.7943	likely_pathogenic	0.7813	pathogenic	-1.54	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/D	0.9938	likely_pathogenic	0.9915	pathogenic	-1.248	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/E	0.9625	likely_pathogenic	0.9486	pathogenic	-1.151	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/F	0.607	likely_pathogenic	0.5156	ambiguous	-1.27	Destabilizing	0.998	D	0.773	deleterious	N	0.468517948	None	None	N
L/G	0.9593	likely_pathogenic	0.9456	pathogenic	-2.461	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/H	0.8888	likely_pathogenic	0.8527	pathogenic	-1.5	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/I	0.129	likely_benign	0.1197	benign	-0.901	Destabilizing	0.81	D	0.592	neutral	None	None	None	None	N
L/K	0.9167	likely_pathogenic	0.8993	pathogenic	-1.496	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
L/M	0.2506	likely_benign	0.2254	benign	-0.846	Destabilizing	0.995	D	0.771	deleterious	N	0.479815482	None	None	N
L/N	0.9548	likely_pathogenic	0.9429	pathogenic	-1.521	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/P	0.8262	likely_pathogenic	0.7386	pathogenic	-1.252	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/Q	0.8592	likely_pathogenic	0.8015	pathogenic	-1.54	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/R	0.8761	likely_pathogenic	0.8381	pathogenic	-0.994	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/S	0.9263	likely_pathogenic	0.8862	pathogenic	-2.283	Highly Destabilizing	0.999	D	0.821	deleterious	N	0.486398848	None	None	N
L/T	0.7428	likely_pathogenic	0.6915	pathogenic	-2.037	Highly Destabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
L/V	0.1002	likely_benign	0.0909	benign	-1.252	Destabilizing	0.102	N	0.383	neutral	N	0.400496838	None	None	N
L/W	0.8557	likely_pathogenic	0.8036	pathogenic	-1.349	Destabilizing	1.0	D	0.78	deleterious	N	0.505263571	None	None	N
L/Y	0.9027	likely_pathogenic	0.87	pathogenic	-1.14	Destabilizing	0.997	D	0.824	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.