TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15642	47149;47150;47151	chr2:178618626;178618625;178618624	chr2:179483353;179483352;179483351
N2AB	14001	42226;42227;42228	chr2:178618626;178618625;178618624	chr2:179483353;179483352;179483351
N2A	13074	39445;39446;39447	chr2:178618626;178618625;178618624	chr2:179483353;179483352;179483351
N2B	6577	19954;19955;19956	chr2:178618626;178618625;178618624	chr2:179483353;179483352;179483351
Novex-1	6702	20329;20330;20331	chr2:178618626;178618625;178618624	chr2:179483353;179483352;179483351
Novex-2	6769	20530;20531;20532	chr2:178618626;178618625;178618624	chr2:179483353;179483352;179483351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-108
• Domain position: 75
• Structural Position: 162
• Q(SASA): 0.826
• Predicted PPI site: I

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
K/T	None	None	0.733	N	0.453	0.305	0.339074221408	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
K/A	0.2937	likely_benign	0.3756	ambiguous	0.051	Stabilizing	0.992	D	0.457	neutral	None	None	None	None	I
K/C	0.6958	likely_pathogenic	0.8194	pathogenic	-0.091	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/D	0.5206	ambiguous	0.5974	pathogenic	-0.133	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
K/E	0.1718	likely_benign	0.2085	benign	-0.125	Destabilizing	0.989	D	0.47	neutral	N	0.502799491	None	None	I
K/F	0.753	likely_pathogenic	0.8535	pathogenic	-0.159	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	I
K/G	0.4503	ambiguous	0.5577	ambiguous	-0.14	Destabilizing	0.996	D	0.433	neutral	None	None	None	None	I
K/H	0.3586	ambiguous	0.4455	ambiguous	-0.399	Destabilizing	1.0	D	0.489	neutral	None	None	None	None	I
K/I	0.2466	likely_benign	0.3213	benign	0.48	Stabilizing	0.997	D	0.595	neutral	N	0.513133294	None	None	I
K/L	0.3501	ambiguous	0.4623	ambiguous	0.48	Stabilizing	0.992	D	0.426	neutral	None	None	None	None	I
K/M	0.2589	likely_benign	0.3481	ambiguous	0.15	Stabilizing	1.0	D	0.497	neutral	None	None	None	None	I
K/N	0.3853	ambiguous	0.4756	ambiguous	0.291	Stabilizing	0.998	D	0.461	neutral	N	0.512114899	None	None	I
K/P	0.4954	ambiguous	0.5208	ambiguous	0.364	Stabilizing	1.0	D	0.49	neutral	None	None	None	None	I
K/Q	0.1411	likely_benign	0.1722	benign	0.15	Stabilizing	0.998	D	0.495	neutral	N	0.511265133	None	None	I
K/R	0.0877	likely_benign	0.1002	benign	-0.016	Destabilizing	0.733	D	0.485	neutral	N	0.510637139	None	None	I
K/S	0.3565	ambiguous	0.461	ambiguous	-0.091	Destabilizing	0.983	D	0.458	neutral	None	None	None	None	I
K/T	0.1601	likely_benign	0.2049	benign	0.056	Stabilizing	0.733	D	0.453	neutral	N	0.511777351	None	None	I
K/V	0.2701	likely_benign	0.347	ambiguous	0.364	Stabilizing	0.998	D	0.434	neutral	None	None	None	None	I
K/W	0.775	likely_pathogenic	0.8681	pathogenic	-0.235	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
K/Y	0.6436	likely_pathogenic	0.7647	pathogenic	0.114	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	I

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.