ClinVar Miner

Submissions for variant NM_000038.6(APC):c.1902T>G (p.Ser634Arg)

dbSNP: rs876659460
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222920 SCV000275959 likely pathogenic Hereditary cancer-predisposing syndrome 2024-01-09 criteria provided, single submitter clinical testing The c.1902T>G variant (also known as p.S634R), located in coding exon 14 of the APC gene, results from a T to G substitution at nucleotide position 1902. The serine at codon 634 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with APC-related disease (Ambry internal data; Grandval P et al. Hum. Mutat. 2014 May; 35(5):532-6; Rohlin A et al. Fam Cancer 2017 Apr;16(2):195-203.). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. This variant was reported to cause exon 14 skipping by mini-gene and RT-PCR RNA analysis (Grandval P et al. Hum. Mutat. 2014 May; 35(5):532-6). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV003335256 SCV003525740 uncertain significance Familial adenomatous polyposis 1 2022-01-17 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 24599579; Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 231954). This missense change has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 27696107). This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 634 of the APC protein (p.Ser634Arg).
Myriad Genetics, Inc. RCV003335256 SCV004044260 likely pathogenic Familial adenomatous polyposis 1 2023-05-03 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data].

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