ClinVar Miner

Submissions for variant NM_001083603.1(PTCH1):c.131A>G (p.Glu44Gly)

gnomAD frequency: 0.00732  dbSNP: rs202111971
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000034685 SCV001764898 likely benign not provided 2019-06-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327)
Fulgent Genetics, Fulgent Genetics RCV002490463 SCV002797264 likely benign Basal cell carcinoma, susceptibility to, 1; Gorlin syndrome; Holoprosencephaly 7 2022-04-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004549404 SCV004771634 benign PTCH1-related disorder 2019-09-05 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000034685 SCV000043461 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
ITMI RCV000121907 SCV000086111 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000121907 SCV001549876 benign not specified no assertion criteria provided clinical testing The PTCH1 p.Glu44Gly variant was identified in dbSNP (ID: rs202111971) and in ClinVar (classified as benign by the Biesecker Lab/Human Development Section, National Institutes of Health) but was not identified in Cosmic or LOVD 3.0. The variant was also identified in control databases in 921 of 277682 chromosomes (13 homozygous) at a frequency of 0.003317 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 526 of 23938 chromosomes (freq: 0.02197), East Asian in 296 of 19242 chromosomes (freq: 0.01538), Other in 17 of 7066 chromosomes (freq: 0.002406), Latino in 55 of 34712 chromosomes (freq: 0.001584), South Asian in 13 of 30206 chromosomes (freq: 0.00043) and European (non-Finnish) in 14 of 127278 chromosomes (freq: 0.00011), while the variant was not observed in the Ashkenazi Jewish and European (Finnish) populations. The variant was identified in 2/177 healthy controls in a study that identified variants in cancer genes in participants without a personal or family history of cancer (Johnston_2012_PMID:22703879). The p.Glu44G residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000034685 SCV001798939 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000034685 SCV001963709 likely benign not provided no assertion criteria provided clinical testing

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