Table 2 The CSF1R mutations reported in BANDDOS

Monies et al. (2017)

c.1620T > A

Tyr540*

Nonsense mutation (Premature stop codon)

Truncated CSF1R protein without intracellular part of the receptor

38

Pathogenic

(PVS1, PM2, PP3, PP4, PP5)

Guo et al. (2019)

c.395 C > T

Pro132Leu

Missense variant

Functionally deficient CSF1R protein

25

Pathogenic

(PS3, PM2, PM3, PP2, PP3, PP4, PP5)

Guo et al. (2019)

c.1441 C > T

Gln481*

Nonsense mutation (Premature stop codon)

Truncated CSF1R protein without intracellular part of the receptor

31

Pathogenic

(PVS1, PS3, PM2, PP3, PP4, PP5)

Guo et al. (2019)

c.1859-119G > A

Ser620delins40

Intronic variant

Splicing mutation generating a novel cryptic splice acceptor site

13

Pathogenic

(PS3, PM1, PM2, PM4, PP1, PP3, PP4, PP5)

Guo et al. (2019);

c.1879_1881del

Lys627del

Inframe deletion

In-frame deletion of lysine in the intracellular kinase domain of CSF1R causing functionally deficient CSF1R protein

Not available

Pathogenic

(PS3, PM1, PM2, PM4. PP3, PP4, PP5)

Guo et al. (2019);

Helman et al. (2020)

c.1969 + 115_1969 + 116del

Pro658Serfs*24

Intronic variant

Splicing mutation leading to the inclusion of the cryptic-exon, resulting in an in-frame stop codon, and nonsense-mediated mRNA decay

Not available

Pathogenic

(PS3, PM1, PM2, PM4, PP3, PP4, PP5)

Oosterhof et al. (2019)

c.1754-1G > C

Gly585_Lys619delinsAla

Splicing mutation

Disruption of a splice acceptor site, leading to skipping of the amino acids 585–619 within the tyrosine kinase domain and production of an in-frame protein product

33

Likely Pathogenic

(PM1, PM2, PM4, PP3, PP4, PP5)

Oosterhof et al. (2019)

c.1929 C > A

His643Gln

Missense variant

Functionally deficient CSF1R protein

4

Likely Pathogenic

(PM1, PM2, PP1, PP2, PP4, PP5)

Tamhankar et al. (2020)

c.2498 C > T

Thr833Met

Missense variant

Functionally deficient CSF1R protein

29

Pathogenic

(PS3, PM1, PM2, PP2, PP3, PP4, PP5)

Kındıs et al. (2021)

c.2763 + 1G > T

Not available

Splicing mutation

Aberrant splicing causing disruption of tyrosine kinase domain

34

*Likely Pathogenic

(PM2, PM4, PP3, PP4, PP5)

Our cases

c.1754G > T

Gly585Val

Splicing mutation^#

Disruption of a splice acceptor site resulting in disruption of tyrosine kinase domain

35

Likely Pathogenic

(PM1, PM2, PM5, PP2, PP3, PP4)